Journal: Frontiers in Pharmacology

Article Title: Cytochrome P450 Enzymes Involved in Metoprolol Metabolism and Use of Metoprolol as a CYP2D6 Phenotyping Probe Drug

doi: 10.3389/fphar.2018.00774

Figure Lengend Snippet: α-Hydroxylation of metoprolol and 1′-hydroxylation of midazolam by CYP3A4 overexpressing supersomes. (A) α-Hydroxylation of metoprolol and 1′-hydroxylation of midazolam. 1′-hydroxylation of midazolam was also determined in the presence of 0.5 μM ketoconazole (CYP3A4 inhibitor). (B) α-hydroxylation of metoprolol in the absence and in the presence of 1 μM quinidine (CYP2D6 inhibitor) or 0.5 μM ketoconazole (CYP3A4 inhibitor). Data are presented as mean ± SD. MDZ: midazolam, MTP: metoprolol.

Article Snippet: 1′-OH-midazolam and midazolam-d6 were acquired from Lipomed (Arlesheim, Switzerland), while rifampicin, ketoconazole, quinidine, and β-glucuronidase (type HP-2 from Helix pomatia ) were obtained from Sigma-Aldrich (Sigma-Aldrich Chemie GmbH, Buchs, Switzerland).

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine

doi: 10.1046/j.1365-2125.2000.00290.x

Figure Lengend Snippet: Mean plasma concentrations of loratadine or desloratadine (DCL) vs time at day 10 steady state in healthy male volunteers taking loratadine alone (○) or in combination (•) with ketoconazole. (a) Loratadine concentrations (ng ml −1 ) vs time (h) after dosing. (b) DCL concentrations (ng ml −1 ) vs time (h) after dosing.

Article Snippet: The ketoconazole (Nizoral®) 200 mg tablets were manufactured by Janssen Pharmaceuticals, Titusville, NJ, and the cimetidine (Tagamet®) 300 mg tablets were manufactured by SmithKline Beecham, Philadelphia, PA. Because the dosage forms used in this study differed, a third-party assigned volunteers to the various treatment groups according to a random code and supervised the administration of assigned treatments to each volunteer.

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine

doi: 10.1046/j.1365-2125.2000.00290.x

Figure Lengend Snippet: Mean change from baseline for maximum value for electrocardiographic parameters. Absolute changes are shown on y axis, ECG parameters are shown on x axis. (a) Ketoconazole interaction study: ▪ loratidine; □ ketoconazole; loratidine + ketoconazole. (b) Cimetidine interaction study: ▪ loratidine; □ cimetidine; loratidine + cimetidine.

Article Snippet: The ketoconazole (Nizoral®) 200 mg tablets were manufactured by Janssen Pharmaceuticals, Titusville, NJ, and the cimetidine (Tagamet®) 300 mg tablets were manufactured by SmithKline Beecham, Philadelphia, PA. Because the dosage forms used in this study differed, a third-party assigned volunteers to the various treatment groups according to a random code and supervised the administration of assigned treatments to each volunteer.

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non-peptide AVP antagonist in healthy subjects

doi: 10.1111/j.1365-2125.2011.04114.x

Figure Lengend Snippet: Tolvaptan (TLV) plasma concentrations following administration of 30 mg alone or with 200 mg ketoconazole to 17 healthy subjects. TLV 30 mg ( ); TLV + ketoconazole ( )

Article Snippet: On days 4, 5 and 6, subjects received a single daily 200 mg tablet of ketoconazole (Janssen Pharmaceutica, Titusville, NJ).

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non-peptide AVP antagonist in healthy subjects

doi: 10.1111/j.1365-2125.2011.04114.x

Figure Lengend Snippet: Ketoconazole trial

Article Snippet: On days 4, 5 and 6, subjects received a single daily 200 mg tablet of ketoconazole (Janssen Pharmaceutica, Titusville, NJ).

Techniques:

Journal: British Journal of Clinical Pharmacology

Article Title: Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non-peptide AVP antagonist in healthy subjects

doi: 10.1111/j.1365-2125.2011.04114.x

Figure Lengend Snippet: Ketoconazole trial

Article Snippet: On days 4, 5 and 6, subjects received a single daily 200 mg tablet of ketoconazole (Janssen Pharmaceutica, Titusville, NJ).

Techniques:

Journal: Pain

Article Title: The Oxidized Linoleic Acid Metabolite-Cytochrome P450 System is Active in Biopsies from Patients with Inflammatory Dental Pain

doi: 10.1016/j.pain.2013.07.011

Figure Lengend Snippet: Biochemical analysis of linoleic acid metabolites generated by inflamed human dental pulp tissues. Normal human dental pulp as well as human dental pulp with irreversible pulpitis (IP) were pretreated with either vehicle or ketoconazole 150μM for 40 min at 37°C prior to application of buffer containing [C 14 ]-linoleic acid 100μM with either ketoconazole 150 μM or vehicle for 1 h at 37°C. The superfusates were collected, lipids extracted and subjected to HPLC/radiometric analysis to quantify the amount of linoleic acid metabolized by each group of tissues. (A) Data are plotted as the mean of the sum of % area under the curve. n=3/group. Error Bar: S.E.M. (B) Representative traces for each treatment group is shown with the peak of unmetabolized [C 14 ]-linoleic acid and oxidized [C 14 ]-labeled linoleic acid metabolites.

Article Snippet: Ketoconazole and iodo-resinferatoxin (I-RTX) were purchased from Tocris (Ellsville, MO).

Techniques: Generated, High Performance Liquid Chromatography, Labeling

Journal: Pain

Article Title: The Oxidized Linoleic Acid Metabolite-Cytochrome P450 System is Active in Biopsies from Patients with Inflammatory Dental Pain

doi: 10.1016/j.pain.2013.07.011

Figure Lengend Snippet: Functional analysis of linoleic acid metabolites generated by inflamed human dental pulp tissues. Normal human dental pulp as well as human dental pulp with irreversible pulpitis (IP) were pretreated with either vehicle or ketoconazole 150μM for 40 min at 37°C prior to application of buffer containing linoleic acid 100μM with either ketoconazole 150 μM or vehicle for 1 h at 37°C. The superfusates were collected, lipids extracted and applied onto one-day old rat trigeminal ganglion neurons for 2 min with inward currents measured using whole-cell patch clamp electrophysiology. Neurons were pretreated with either ketoconazole 30μM or the combination of ketoconazole 30μM and the TRPV1 antagonist I-RTX 100nM for 15 min prior to application of tissue extracts. n= 8-10 tissue samples were used and extracts were applied over five different neuronal cultures. (A) Data are plotted as the mean of all the peak currents generated by each group after extract application. Error Bar: S.E.M. (B) Representative traces for each group is shown.

Article Snippet: Ketoconazole and iodo-resinferatoxin (I-RTX) were purchased from Tocris (Ellsville, MO).

Techniques: Functional Assay, Generated, Patch Clamp

Journal: Molecular Pain

Article Title: The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid metabolite-mediated peripheral inflammatory pain

doi: 10.1186/1744-8069-8-73

Figure Lengend Snippet: Effect of Ketoconazole on CFA-induced Thermal Allodynia. A 50uL solution of 1:1 CFA:saline was injected into the right hind paw of rats and 24 hours later, heat hyperalgesia was measured using the radiant heat test in the inflamed paws as well as in the contralateral paws. As noted, ketoconazole (4ug) was injected 30 sec prior to CFA injection and 24 hours later, thermal allodynia was measured in the A. inflamed paw and in the contralateral paw, following which another injection of ketoconazole (4ug) was injected in the inflamed paw. Heat hyperalgesia was tested at 30 and 60 minutes after second injection in the A inflamed paw and in the contralateral paw. In a separate group of animals, vehicle was injection 30 seconds prior to CFA injection. Heat hyperalgesia tested at 24 hours in the B. inflamed as well as contralateral paws, following which another vehicle injection was given and heat hyperalgesia tested at 30 and 60 minutes in the B. inflamed as well as in the contralateral paws. For data set C and D , the experiment was performed in the similar fashion as 2A and B, except C. ketoconazole or D. vehicle was injected in the un-inflamed paw and heat hyperalgesia measured in ipsilateral paw (inflamed) as well as contralateral paw, 30 and 60 minutes after second injection. n = 6 was used for each group in all the experiments and mean of all n’s is plotted. Data were analyzed using one-way ANOVA with Neuman-Keuls Post-hoc test. Error Bar: S.E.M.

Article Snippet: Drugs Ketoconazole, iodo-resinferatoxin (I-RTX) and capsazepine (CPZ) were purchased from Tocris (Ellsville, Missouri, USA).

Techniques: Injection, Size-exclusion Chromatography

Journal: Molecular Pain

Article Title: The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid metabolite-mediated peripheral inflammatory pain

doi: 10.1186/1744-8069-8-73

Figure Lengend Snippet: Effect of anti-HODE Antibodies and Ketoconazole on LA-evoked Nocifensive Behavior. A. Rats were injected with 1:1CFA and 24 hours later, were injected with either vehicle, control IgG anti-goat antibody or mix of anti-9 and 13-HODE antibodies (25ug each). Following 10 minutes, a second injection of either vehicle or 1000ug LA was given and nocifensive behavior was recorded upto 15 mins. Data plotted is the total nocifensive time (secs) observed between 8 and 15 mins. n = 8/10 was used for each group. Data analyzed using one-way ANOVA with Neuman-Keuls post hoc test. Error Bar: S.E.M. B. Similar to data set 4A, rats were injected with vehicle or 4ug ketoconazole as the first injection into the inflamed paws and 30 minutes later, vehicle or 1000ug LA with vehicle or 1000ug LA with 4ug ketoconazole was given as the second injection. Data plotted is the total nocifensive time (secs) observed between 8 and 15 mins. n = 8/10 was used for each group. Data Analyzed using one-way ANOVA with Neuman-Keuls post hoc test. Error Bar: S.E.M.

Article Snippet: Drugs Ketoconazole, iodo-resinferatoxin (I-RTX) and capsazepine (CPZ) were purchased from Tocris (Ellsville, Missouri, USA).

Techniques: Injection

Journal: Molecular Pain

Article Title: The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid metabolite-mediated peripheral inflammatory pain

doi: 10.1186/1744-8069-8-73

Figure Lengend Snippet: Release of TRPV1 agonists. A. Twenty-four hour old rat TG cultures were pretreated with either vehicle or 30uM ketoconazole for 15 minutes following which 1 mM LA with vehicle or the same concentration of ketoconazole was applied to the neurons for 2 minutes and calcium accumulated was tested by measuring ratio of fluorescence produced at 340 and 380 nm wavelengths. The experiment was performed with three independent neuronal cultures and mean responses for each group is plotted. Data were analyzed using 2-tailed student’s t -test. Error Bars: S.E.M. Noise indicates basal fluorescence ratio 340/360 with application of Hanks Buffer. B. Lipophilic extracts were made from inflamed skin from rats, pretreated with vehicle or 18 mM ketoconazole in vivo as well as vehicle or 150uM ketoconazole ex vivo and applied onto 5-day old rat TG cultures for 15 minutes. Neurons were pretreated with either vehicle or 1uM I-RTX for 15 minutes prior to extract application. The superfusates were collected and subjected to radioimmunoassay for estimation of CGRP release. Three independent experiments were performed and data plotted is the mean of % release from baseline for each group. Data were normalized such that baseline release from neurons was made to be 100%. Data were analyzed using one-way ANOVA and Neuman-Keuls post hoc test. Error Bars: S.E.M.

Article Snippet: Drugs Ketoconazole, iodo-resinferatoxin (I-RTX) and capsazepine (CPZ) were purchased from Tocris (Ellsville, Missouri, USA).

Techniques: Concentration Assay, Fluorescence, Produced, In Vivo, Ex Vivo, RIA Assay

Journal: The Prostate

Article Title: Of Mice and Men-Warning: Intact Versus Castrated Adult Male Mice as Xenograft Hosts Are Equivalent to Hypogonadal Versus Abiraterone Treated Aging Human Males, Respectively

doi: 10.1002/pros.22677

Figure Lengend Snippet: Response of castrate resistant human CWR-22RH xenograft inoculated into castrated adult male nude mice to the CYP17A1 inhibitor, ketoconazole (N = 10 per group). Ketoconazole was given 5 days per week via oral gavage at a dose of 25 mg/kg.

Article Snippet: Ketoconazole was obtained from LKT Laboratories, Inc. (St. Paul, MN).

Techniques: Mouse Assay

Journal: Scientific Reports

Article Title: Identification of Novel Inhibitors of DLK Palmitoylation and Signaling by High Content Screening

doi: 10.1038/s41598-019-39968-8

Figure Lengend Snippet: Dose-dependent inhibition of DLK-GFP localization and palmitoylation by ketoconazole. ( A ) Quantified DLK puncta per transfected cell from HEK293T cells transfected as in Fig. 2 and treated with the indicated concentrations of ketoconazole. Data (mean ± SEM) are plotted relative to DMSO vehicle control for 6 fields of view per condition from 8 determinations per condition. ***p

Article Snippet: Fresh Ketoconazole stock for follow-up assays was from LKT Laboratories (Catalog #K1676).

Techniques: Inhibition, Transfection

Journal: Scientific Reports

Article Title: Identification of Novel Inhibitors of DLK Palmitoylation and Signaling by High Content Screening

doi: 10.1038/s41598-019-39968-8

Figure Lengend Snippet: Ketoconazole inhibits palmitoylation of DLK and PSD-95, but not GAP43. ( A ) HEK293T cells were transfected with DLK-GFP cDNA and incubated with 20 µM 2BP, or with 2.5 µM or 5 µM ketoconazole 2 h post-transfection for 16–18 h. Upper western blot shows DLK total expression and palmitoyl-DLK levels (from ABE, ‘HAM+’) for each condition. A negative control sample was generated by combining equal fractions of lysates from all conditions, which was then subjected to ABE in the absence of the key reagent hydroxylamine (HAM-). Lower western blot shows tubulin levels, an indication of total protein expression. Molecular weight markers are indicated on each blot. Differing band widths in this panel are likely due to different protein concentrations and/or ionic strength of total lysates versus ABE fractions. ( B ) Histogram of pooled data (mean ± SEM) for 4 determinations per condition from A . Ketoconazole and 2BP both significantly reduce DLK palmitoylation. Some data from this panel are re-plotted as part of Fig. 3D . ( C ) As A , except that cells were transfected with GAP43-Myc cDNA ABE fractions were blotted with anti-Myc antibody and cell lysates were blotted to detect total expression of GAP43-myc (upper panel) and GAPDH (lower panel). ( D ) Histogram of pooled data (mean ± SEM) for 7 determinations per condition from C . Ketoconazole does not reduce GAP43 palmitoylation, but 2BP does. ( E ) As C , except that cells were transfected with PSD-95 cDNA and total lysates and ABE fractions were blotted with anti-PSD-95 antibody. ( F ) Histogram of pooled data (mean ± SEM) for 4 determinations per condition from E . 5 μM ketoconazole and 2BP both reduce PSD-95 palmitoylation. One-way ANOVA, Kruskal-Wallis post-hoc analysis; ( A ) ANOVA p = 0.0009, h = 13.92, ( C ) ANOVA not significant, ( E ) ANOVA p = 0.0158, h = 8.290.

Article Snippet: Fresh Ketoconazole stock for follow-up assays was from LKT Laboratories (Catalog #K1676).

Techniques: Transfection, Incubation, Western Blot, Expressing, Negative Control, Generated, Molecular Weight

Journal: Scientific Reports

Article Title: Identification of Novel Inhibitors of DLK Palmitoylation and Signaling by High Content Screening

doi: 10.1038/s41598-019-39968-8

Figure Lengend Snippet: Ketoconazole significantly decreases DLK-mediated phospho-cJun activation in primary neurons. ( A ) Dorsal Root Ganglion (DRG) neurons were treated at 7 Days in vitro (DIV 7) with 2.5 µM Ketoconazole overnight or 20 µM 2BP for 2 h prior to a 2.5 h NGF withdrawal in presence of the indicated compound. Cells were lysed in SDS-PAGE loading buffer and levels of endogenous DLK, phospho-cJun (p-cJun) and tubulin were detected by western blot as indicated. The secondary antibody used on the p-cJun blot also weakly recognizes residual anti-NGF IgG used as part of the trophic factor deprivation (indicated by asterisk). ( B ) Quantification of phospho-cJun normalised to –NGF vehicle-treated cells. Two-way ANOVA indicates significant effects of interaction (p = 0.0071), NGF (p = 0.0026) and Ketoconazole (p = 0.0001). The effect of Ketoconazole in DRGs undergoing NGF withdrawal was also significant as determined by the Bonferroni post-test (p

Article Snippet: Fresh Ketoconazole stock for follow-up assays was from LKT Laboratories (Catalog #K1676).

Techniques: Activation Assay, In Vitro, SDS Page, Western Blot

Journal: Scientific Reports

Article Title: Identification of Novel Inhibitors of DLK Palmitoylation and Signaling by High Content Screening

doi: 10.1038/s41598-019-39968-8

Figure Lengend Snippet: A High Content Imaging screen identifies ketoconazole as the most potent compound to inhibit DLK-GFP puncta formation. ( A ) HEK293T cells cotransfected with DLK-GFP plus mCherry-NLS were treated with 2BP or vehicle and fixed to detect GFP, mCherry and the nuclear marker DAPI. 2BP reduces DLK-GFP puncta without affecting mCherry-NLS expression or DAPI signal. Scale bar: 25 µm. ( B ) HEK293T cells were seeded into 12 wells of a 96-well plate and transfected with DLK-GFP and NLS-mCh cDNA and then treated with 2BP (20 μM in DMSO) or 0.1% (v/v) DMSO vehicle as in A . Cells were fixed and imaged using an ImageXpress High Content Imaging system to detect GFP and NLS-mCh signals. Assay quality was determined by calculating the z-prime (z′) for 6 determinations per condition (z′ = S/R, S = [(Mean of Vehicle treated – 3xSD)-(Mean of 2BP – 3xSD)], R = Vehicle Mean – 2BP mean). ( C ) Design of the high-throughput screen for compounds that inhibit DLK-GFP punctate localization. ( D ) The effect of 1200 compounds from the Prestwick Chemical Library™ on DLK puncta per transfected cell (mean of 2 determinations per compound) was calculated using ImageXpress Image Analysis ‘TransFluor’ and Multi-Wavelength Scoring (MWS) modules. Compounds that decreased the number of transfected cells (from mCherry-NLS count) or the total number of cells (from DAPI count) by greater than 30%, relative to the mean of vehicle treated controls, are not plotted due to likely cytotoxicity or non-specific effects. Red and blue lines indicate 3 standard deviations (3 SD) above and below the mean of all determinations, respectively. Compounds that decreased DLK puncta per transfected cell below this 3 SD cut-off were considered ‘Hits’. The most potent ‘hit’, ketoconazole, is highlighted in red.

Article Snippet: Fresh Ketoconazole stock for follow-up assays was from LKT Laboratories (Catalog #K1676).

Techniques: Imaging, Marker, Expressing, Transfection, High Throughput Screening Assay

Journal: Journal of Drug Assessment

Article Title: Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers

doi: 10.3109/21556660.2013.785413

Figure Lengend Snippet: Mean (± standard deviation) plasma concentration–time profiles of ticagrelor (a) and AR-C124910XX (b) following a single 90-mg oral dose of ticagrelor in the presence and absence of ketoconazole (200 mg twice daily) ( n = 17).

Article Snippet: The LOQ for diltiazem was 1 ng/mL, and 10 ng/mL for ketoconazole (AstraZeneca, data on file).

Techniques: Standard Deviation, Concentration Assay

Journal: International Journal of Nanomedicine

Article Title: Size- and shape-dependent clinical and mycological efficacy of silver nanoparticles on dandruff

doi: 10.2147/IJN.S86828

Figure Lengend Snippet: Skin photographs of the dorsal surface of rats. Notes: ( A ) Control group I showing no redness, no inflammation; ( B ) M. furfur diseased group, scales on the skin; ( C ) and ( D ) Groups III and IV treated with itracanozole and ketoconazole, respectively, showing skin with decreased scales as compared to Group II with pinkish color; ( E ) Group V (20 nm spherical Ag NPs) showing complete treatment of M. furfur as compared to Group II; ( F ) and ( G ) Groups VI and VII (50 nm spherical- and rod-shaped Ag NPs) also showed normalization of the skin but less as compared to group V. Abbreviations: M. furfur , Malassezia furfur ; NPs, nanoparticles.

Article Snippet: Antifungal drugs such as itraconazole and ketoconazole were obtained from HiMedia Laboratories Pvt.

Techniques:

Journal: International Journal of Nanomedicine

Article Title: Size- and shape-dependent clinical and mycological efficacy of silver nanoparticles on dandruff

doi: 10.2147/IJN.S86828

Figure Lengend Snippet: Histopathological microphotographs of different groups of studied rats. Notes: ( A ) Control I; ( B ) M. furfur diseased model group II; antifungal agent-treated groups; ( C ) III (itracanozole); ( D ) IV (ketoconazole); ( E ) V (20 nm spherical-shaped Ag NPs); ( F ) VI (50 nm spherical), and ( G ) VII (50 nm rod-shaped Ag NPs). Abbreviations: M. furfur , Malassezia furfur ; NPs, nanoparticles.

Article Snippet: Antifungal drugs such as itraconazole and ketoconazole were obtained from HiMedia Laboratories Pvt.

Techniques:

Journal: Drug Design, Development and Therapy

Article Title: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

doi: 10.2147/DDDT.S73476

Figure Lengend Snippet: Chemical structures of Xyloketal B, midazolam, ketoconazole, and probucol.

Article Snippet: Ketoconazole was obtained from Nanjing Pharmaceutical Co (Baijingyu, People’s Republic of China, catalog number 65277-42-1).

Techniques:

Journal: Drug Design, Development and Therapy

Article Title: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

doi: 10.2147/DDDT.S73476

Figure Lengend Snippet: Effect of consecutive administration of XKB on the pharmacokinetics of 1′-OH-MDZ in rats. Notes: Plasma concentration-time profiles of MDZ up to 6 hours after 8 consecutive days of intraperitoneal injection of XKB (14 mg/kg, ♦), XKB (7 mg/kg, ▼), soybean oil(■), or physiological saline (•), and oral administration of KTZ (75 mg/kg, ▲), followed on day 9 by oral administration of MDZ 20 mg/kg. Data represent the mean ± standard deviation (n=8). Abbreviations: XKB, Xyloketal B; MDZ, midazolam; KTZ, ketoconazole.

Article Snippet: Ketoconazole was obtained from Nanjing Pharmaceutical Co (Baijingyu, People’s Republic of China, catalog number 65277-42-1).

Techniques: Concentration Assay, Injection, Standard Deviation

Journal: Drug Design, Development and Therapy

Article Title: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

doi: 10.2147/DDDT.S73476

Figure Lengend Snippet: Molecular interactions between XKB, MDZ, KTZ, and probucol and the rat Cyp3a2 homology model. Notes: The rat Cyp3a2 homology model was established based on human CYP3A4 structure available in PDB (PDB ID 4K9W).( A ) Molecular interactions between XKB and rat Cyp3a2 homology model. ( B ) Molecular interactions between MDZ and the rat Cyp3a2 homology model. ( C ) Molecular interactions between KTZ and the rat Cyp3a2 homology model. ( D ) Molecular interactions between probucol and rat Cyp3a2 homology model. Abbreviations: XKB, Xyloketal B; MDZ, midazolam; KTZ, ketoconazole; CYP, cytochrome P450; PDB, Protein Data Bank.

Article Snippet: Ketoconazole was obtained from Nanjing Pharmaceutical Co (Baijingyu, People’s Republic of China, catalog number 65277-42-1).

Techniques:

Journal: Drug Design, Development and Therapy

Article Title: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

doi: 10.2147/DDDT.S73476

Figure Lengend Snippet: Effects of consecutive administration for 8 days of XKB on the pharmacokinetics of MDZ in rats. Notes: Plasma concentration-time profiles of MDZ up to 6 hours after 8 consecutive days of intraperitoneal injection of XKB (14 mg/kg, ♦), XKB (7 mg/kg, ▼), soybean oil (■), or physiological saline (•), and oral administration of KTZ (75 mg/kg, ▲), followed on day 9 by oral administration of MDZ 20 mg/kg. Data represent the mean ± standard deviation (n=8). Abbreviations: XKB, Xyloketal B; MDZ, midazolam; KTZ, ketoconazole.

Article Snippet: Ketoconazole was obtained from Nanjing Pharmaceutical Co (Baijingyu, People’s Republic of China, catalog number 65277-42-1).

Techniques: Concentration Assay, Injection, Standard Deviation

Journal: Drug Design, Development and Therapy

Article Title: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

doi: 10.2147/DDDT.S73476

Figure Lengend Snippet: Molecular interactions between XKB, MDZ, KTZ, and probucol and human CYP3A4. Notes: The human CYP3A4 structure was selected from PDB database (PDB ID 4K9W). ( A ) Molecular interactions between XKB and human CYP3A4. ( B ) Molecular interactions between MDZ and human CYP3A4. ( C ) Molecular interactions between KTZ and human CYP3A4. ( D ) Molecular interactions between probucol and human CYP3A4. Abbreviations: XKB, Xyloketal B; MDZ, midazolam; KTZ, ketoconazole; CYP, cytochrome P450; PDB, Protein Data Bank.

Article Snippet: Ketoconazole was obtained from Nanjing Pharmaceutical Co (Baijingyu, People’s Republic of China, catalog number 65277-42-1).

Techniques:

Journal: Human Molecular Genetics

Article Title: Analysis of hedgehog signaling in cerebellar granule cell precursors in a conditional Nsdhl allele demonstrates an essential role for cholesterol in postnatal CNS development

doi: 10.1093/hmg/ddv042

Figure Lengend Snippet: Effects of LDL and ketoconazole treatment on Nsdhl flx5 /Y and Nsdhl Δ5 /Y GCPs in vitro . GCPs were isolated from individual cerebella at P4, split into 4 culture wells with the indicated treatments and analyzed after 48 h. All samples received 1

Article Snippet: GCPs were plated at a density of 2.5 × 105 cells/cm2 on poly-D-lysine coated 6-well or 12-well tissue culture plates (Corning, Corning, NY) in 3 or 1 ml respectively of serum-free culture medium (SFM), consisting of Neurobasal-A medium (Life Technologies, Carlsbad, CA) supplemented with GlutaMAX I (Life Technologies), 250 μ m KCl, 50 I.U./ml penicillin, 50 μg/ml streptomycin and B-27 supplement (Life Technologies) and cultured at 37°C, 5% CO2 for 48 h. Where indicated, SFM was supplemented with 15 μg/ml cholesterol (Sigma) from a 15 mg/ml stock solution in 95% ethanol, 1 μg/ml recombinant mouse sonic hedgehog N-terminus (SHH-N) (R & D Systems, Minneapolis, MN) from a 100 μg/ml stock solution in 1% BSA in PBS, 5 μg/ml human LDL (Biomedical Technologies, Stoughton, Ma) from a 5 mg/ml stock solution, 2 μ m ketoconazole (Santa Cruz Biotechnology, Santa Cruz, CA) from a 1 m m stock in DMSO, and/or 100 n m smoothened agonist, SAG (EMD Millipore, Billerica, MA) from a 100 m m stock in DMSO.

Techniques: In Vitro, Isolation

Journal: Biochemical pharmacology

Article Title: The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent

doi: 10.1016/j.bcp.2014.07.007

Figure Lengend Snippet: Effect of ketoconazole on the metabolism of PSA in liver microsomes PSA (50 μM) was incubated with or without ketoconazole in mouse or human liver microsomes) at 37°C for 1h. PSA metabolites were extracted and assayed using HPLC. Presented are the percentages of control at the indicated ketoconazole concentrations.

Article Snippet: Quinidine and ketoconazole were purchased from Toronto Research Chemicals (North York, ON, Canada).

Techniques: Incubation, High Performance Liquid Chromatography

Journal: Pharmaceutics

Article Title: Myth or Truth: The Glass Forming Ability Class III Drugs Will Always Form Single-Phase Homogenous Amorphous Solid Dispersion Formulations

doi: 10.3390/pharmaceutics11100529

Figure Lengend Snippet: Overlay of PXRD patterns and mDSC thermograms of different ASDs samples of ( a , b ) Felodipine, ( c , d ) Indomethacin, and ( e , f ) Ketoconazole.

Article Snippet: Indomethacin and Ketoconazole were purchased from Alfa Aesar, Kandel, Germany and Acros Organics, Geel, Belgium, respectively.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Mechanism of Amphotericin B Resistance in Leishmania donovani Promastigotes

doi:

Figure Lengend Snippet: Proposed biosynthetic pathway of ergosterol in L. donovani . Symbols: →, pathway of wild-type promastigotes; ⇒, pathway of AmB-resistant promastigotes; ▪, sites inhibited by ketoconazole; ……→, defective 24-methyltransferase in AmB-resistant promastigotes.

Article Snippet: Ketoconazole was purchased from ICN Biomedicals (Orsay, France).

Techniques:

Journal: Journal of Bacteriology

Article Title: Activity of the Kluyveromyces lactis Pdr5 Multidrug Transporter Is Modulated by the Sit4 Protein Phosphatase

doi: 10.1128/JB.183.13.3939-3948.2001

Figure Lengend Snippet: Physical map of the K. lactis chromosomal region containing the KlPDR5 gene and the MDR phenotype conferred by KlPDR5 overexpression. (A) Restriction map of the overlapping genomic clones pROM1/1 and pROM1/8. Open box, KlPDR5 open reading frame; arrow, direction of transcription. (B) Growth and MDR phenotype of K. lactis cells overexpressing KlPDR5 . The strain PM6-7A (wild type) was transformed with pROM1/1 and pROM1/8. The Ura + transformants were diluted to 5 × 10 4 cells/ml, and 10-μl aliquots were applied to GlyYP, GlyYP supplemented with oligomycin (Oli; 0.5 μg/ml) and antimycin (Ant; 0.2 μM), GYP, and GYP supplemented with ketoconazole (Keto; 4.0 μg/ml) and econazole (Eco; 0.2 μg/ml). The plates were incubated at 28°C for 4 days before being photographed.

Article Snippet: The stock solution for ketoconazole (ICN Pharmaceuticals) was prepared with dimethyl sulfoxide.

Techniques: Over Expression, Clone Assay, Transformation Assay, Incubation

Journal: Journal of Bacteriology

Article Title: Activity of the Kluyveromyces lactis Pdr5 Multidrug Transporter Is Modulated by the Sit4 Protein Phosphatase

doi: 10.1128/JB.183.13.3939-3948.2001

Figure Lengend Snippet: Growth and drug sensitivity of K. lactis strains showing the drug-hypersensitive phenotypes of KlPDR5 -disruption strains and the genetic interaction between KlPDR5 and SIT4 . Cells were grown in liquid GYP medium and diluted to 5 × 10 4 /ml, and 10-μl aliquots were applied to GlyYP or GYP supplemented with antimycin (Ant), oligomycin (Oli), econazole (Eco), and ketoconazole (Keto). Photographs were taken after incubation of plates at 28°C for 4 days.

Article Snippet: The stock solution for ketoconazole (ICN Pharmaceuticals) was prepared with dimethyl sulfoxide.

Techniques: Incubation

Journal: The Journal of Physiology

Article Title: Characterization of the putative chloride channel xClC-5 expressed in Xenopus laevis oocytes and comparison with endogenous chloride currents

doi: 10.1111/j.1469-7793.1998.379bh.x

Figure Lengend Snippet: Comparison of the characteristics of I native , I β-globin and I Cl,swell The relative anion conductivity of I Cl,swell . * Inhibition by DIDS, NPPB, DPC, cAMP, oxonol, 9-AC, ketoconazole, gossypol and lanthane.

Article Snippet: Ketoconazole was from Biomol Research Laboratories, Inc. (Plymouth Meeting, PA, USA).

Techniques: Inhibition

Journal: British Journal of Clinical Pharmacology

Article Title: Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity

doi: 10.1046/j.1365-2125.1999.00053.x

Figure Lengend Snippet: Steady-state serum concentration-time profiles of tolterodine in the absence (a) and presence (b) of ketoconazole, 200 mg once daily, after 1 mg twice-daily administration of tolterodine l-tartrate to subjects with deficient CYP2D6 activity.

Article Snippet: After a wash-out period of at least 4 days, each volunteer then received ketoconazole (Fungoral®, Janssen-Cilag) 200 mg once daily for 4 days, and tolterodine as a 2 mg single dose on day 2.

Techniques: Concentration Assay, Activity Assay

Journal: Indian Journal of Pharmacology

Article Title: Interaction potential of Trigonella foenum graceum through cytochrome P450 mediated inhibition

doi: 10.4103/0253-7613.165179

Figure Lengend Snippet: Fluorescence assay. Percentage inhibitory effect of Trigonella foenum graecum extract, trigonelline and positive controls on drug metabolizing enzymes cytochrome P3A4 and cytochrome P2D6 (values are mean ± standard error of the mean; n = 3). Ketoconazole dimethyl sulphoxide = ketoconazole dissolved in dimethyl sulphoxide, ketoconazole ethanol = ketoconazole dissolved in ethanol, TFG DMSO = Trigonella foenum graecum dissolved in dimethyl sulphoxide, TFG ethanol = Trigonella foenum graecum dissolved in ethanol, trigonelline DMSO = trigonelline dissolved in dimethyl sulphoxide, trigonelline ethanol = trigonelline dissolved in ethanol, quinidine DMSO = quinidine dissolved in dimethyl sulphoxide, quinidine ethanol = quinidine dissolved in ethanol

Article Snippet: Ketoconazole and quinidine were obtained from Merck (Mumbai, India).

Techniques: Fluorescence

Journal: G3: Genes|Genomes|Genetics

Article Title: Activation of the Pleiotropic Drug Resistance Pathway Can Promote Mitochondrial DNA Retention by Fusion-Defective Mitochondria in Saccharomyces cerevisiae

doi: 10.1534/g3.114.010330

Figure Lengend Snippet: The PDR1-249 allele dominantly suppresses mitochondrial DNA (mtDNA) loss from mutants unable to fuse mitochondria and activates the PDR pathway. (A) PDR1-249 dominantly allows mtDNA maintenance in cells lacking FZO1 . Strains CDD71 ( fzo1∆ aac2∆ ), CDD664 ( fzo1∆ aac2∆ PDR1-249 ), CDD703 ( fzo1∆/fzo1∆ aac2∆/aac2∆ PDR1/PDR1 ), CDD704 ( fzo1∆/fzo1∆ aac2∆/aac2∆ PDR1-249/PDR1 ), and CDD687 ( fzo1∆ aac2∆ fis1∆ ), all also homozygous for the cyh2 allele and carrying plasmid b19 (p FZO1-CYH2 ), were treated as in Figure 2A . (B) Deletion of PDR1 does not suppress mtDNA loss from cells lacking mitochondrial fusion. Strains CDD71 ( fzo1∆ aac2∆ ), CDD664 ( fzo1∆ aac2∆ PDR1-249 ), and CDD672 ( fzo1∆ aac2∆ pdr1∆ ), all also mutated at the CYH2 locus and carrying plasmid b19 (p FZO1-CYH2 ), were treated as in Figure 2A . (C) Plasmid-borne PDR1-249 can suppress mtDNA loss from fzo1∆ cells. fzo1∆ aac2∆ strain CDD67, also harboring a chromosomal cyh2 mutation and plasmid b19 (p FZO1-CYH2 ), was transformed with empty vector pRS313 ( Sikorski and Hieter 1989 ), plasmid b60 (p PDR1 ), or plasmid b65 (p PDR1-249 ). Transformants were cultured overnight in SC-Trp medium, then again overnight in SMM-His medium before an assay for proliferation following FZO1 loss as in Figure 2A . (D) The PDR1-249 allele activates the PDR pathway. Strains CDD642 ( WT ), CDD658 ( PDR1-249 ), and CDD692 ( fis1∆ ) were cultured overnight in YEPD at 30°, then serially diluted and spotted to YEPD medium alone (no drug) for 1 d at 30°, YEPD containing 0.2 µg/mL CHX for 3 d, or YEPD containing 2 µg/mL ketoconazole for 3 d.

Article Snippet: Ketoconazole (Tokyo Chemical Industry Co., Tokyo, Japan), another PDR substrate, was used at a concentration of 2 µg/mL in YEPD.

Techniques: Plasmid Preparation, Mutagenesis, Transformation Assay, Cell Culture