Journal: Frontiers in Pharmacology

Article Title: Vitamin D Deficiency Impacts Exposure and Response of Pravastatin in Male Rats by Altering Hepatic OATPs

doi: 10.3389/fphar.2022.841954

Figure Lengend Snippet: Study design of pharmacodynamic and pharmacokinetic experiments in rats. Pharmacodynamic study: pharmacodynamic study of pravastatin in VD-sufficient (Control, Control + P) or VD-deficient (VD-deficient, VD-deficient + P) rats. Pharmacokinetic study: pharmacokinetic study of pravastatin in VD-sufficient (Control) or VD-deficient rats. Control: rats fed on a VD-supplement diet with or without gavage of water; VD-deficient: rats fed on a VD-free diet with or without gavage of water; Control + P: rats fed on a VD-supplement diet and administered pravastatin via gavage for 15 days; VD-deficient + P: rats fed on a VD-free diet and administered pravastatin via gavage for 15 days.

Article Snippet: Briefly (but detailed below), rats for pharmacodynamic study were fed on a VD-free/supplement high-fat diet for 25–30 days, followed by gavage of water/pravastatin for 15 days; plasma 25(OH)VD levels were dynamically monitored, and blood lipid was measured before and after gavage of water/pravastatin (A08D8L50107, 98%, Shanghai Yuanye Bio-technology Co., Ltd.).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Vitamin D Deficiency Impacts Exposure and Response of Pravastatin in Male Rats by Altering Hepatic OATPs

doi: 10.3389/fphar.2022.841954

Figure Lengend Snippet: Effect of vitamin D deficiency on the pravastatin efficacy in rats. (A) Final 25(OH)VD 2 , 25(OH)VD 3 and total 25(OH)VD concentration in rats fed on a VD-supplement/free high-fat diet with/without pravastatin. 25(OH)VD 3 and total 25(OH)VD in VD-sufficient rats were higher than VD-deficient rats, and 25(OH)VD 2 was lower ( p < 0.05). (B) Percentage of blood lipid change (TG, TC, and HDL) in rats fed on a VD-supplement/free high-fat diet with/without pravastatin. Among the four groups, TG and TC levels in rats fed on a VD-supplementation diet and treated with pravastatin (Control + P) decreased the most, whereas HDL-C/TC increased the most. TG and TC levels in VD-sufficient rats were lower than in VD-deficient rats, while HDL-C/TC was higher. Control: rats fed on a VD-supplement high-fat diet ( n = 7); VD-deficient: rats fed on a VD-free high-fat diet ( n = 7); Control + P: rats fed on a VD-supplement high-fat diet and administered pravastatin via gavage for 15 days ( n = 7); VD-deficient + P: rats fed on a VD-free high-fat diet and administered pravastatin via gavage for 15 days ( n = 9). TG: triglycerides, TC: total cholesterol, HDL-C: high-density lipoprotein cholesterol. Y-axis: Percentage of blood lipid change = (blood lipid 15 days after administration—blood lipid before administration)/blood lipid before administration, * p < 0.05: statistically significant difference, using ANOVA followed by Tukey’s post-hoc test.

Article Snippet: Briefly (but detailed below), rats for pharmacodynamic study were fed on a VD-free/supplement high-fat diet for 25–30 days, followed by gavage of water/pravastatin for 15 days; plasma 25(OH)VD levels were dynamically monitored, and blood lipid was measured before and after gavage of water/pravastatin (A08D8L50107, 98%, Shanghai Yuanye Bio-technology Co., Ltd.).

Techniques: Concentration Assay

Journal: Frontiers in Pharmacology

Article Title: Vitamin D Deficiency Impacts Exposure and Response of Pravastatin in Male Rats by Altering Hepatic OATPs

doi: 10.3389/fphar.2022.841954

Figure Lengend Snippet: The effect of vitamin D deficiency on the lipid-lowering efficacy of pravastatin (percentage of blood lipid change) in rats.

Article Snippet: Briefly (but detailed below), rats for pharmacodynamic study were fed on a VD-free/supplement high-fat diet for 25–30 days, followed by gavage of water/pravastatin for 15 days; plasma 25(OH)VD levels were dynamically monitored, and blood lipid was measured before and after gavage of water/pravastatin (A08D8L50107, 98%, Shanghai Yuanye Bio-technology Co., Ltd.).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Vitamin D Deficiency Impacts Exposure and Response of Pravastatin in Male Rats by Altering Hepatic OATPs

doi: 10.3389/fphar.2022.841954

Figure Lengend Snippet: Pravastatin pharmacokinetic study results in rats. (A) Plasma 25(OH)VD concentration after feeding for 25 days with a VD-supplement diet (Control group, n = 6) or a VD-free diet (VD-deficient, n = 9). Plasma 25(OH)VD concentration in the deficient group fed on a VD 3 -free diet was lower than that of the control group (13.2 ± 6.26 ng/ml vs. 74.98 ± 22.30 ng/ml). (B) Pravastatin pharmacokinetics parameters. AUC inf in the VD-deficient group is slightly higher, but both AUC inf and C max are not significantly different in the control and VD-deficient group. (C) Pravastatin time profile concentration of control and deficient groups. AUC inf : area under the curve from the time of dosing extrapolated to infinity, C max : maximum plasma concentration. p < 0.05: statistically significant difference, using two-tailed unpaired t-test.

Article Snippet: Briefly (but detailed below), rats for pharmacodynamic study were fed on a VD-free/supplement high-fat diet for 25–30 days, followed by gavage of water/pravastatin for 15 days; plasma 25(OH)VD levels were dynamically monitored, and blood lipid was measured before and after gavage of water/pravastatin (A08D8L50107, 98%, Shanghai Yuanye Bio-technology Co., Ltd.).

Techniques: Concentration Assay, Two Tailed Test