Journal: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics

Article Title: Physiologically based pharmacokinetic modeling (PBPK’s) prediction potential in clinical pharmacology decision making during pregnancy

doi: 10.1002/ijgo.13150

Figure Lengend Snippet: Drug physico-chemical parameters for bictegravir and doravirine.

Article Snippet: 3 , 4 Integrating the physico-chemical characteristics of BIC and DOR ( ) with other in-vitro, ex-vivo, and in-vivo data would allow for the development of a PBPK model to predict maternal and fetal BIC and DOR PK in healthy pregnant women and those with pre-existing disease. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Physico-chemical parameters for bictegravir and doravirine Doravirine Bictegravir Parameters Value Reference [ 3 ] Value Reference [ 4 ] MW (g/Mol) 425.7 Pharmacokinetic summary (Merck) 449.4 Pharmacokinetic summary (Gilead) Log-P o:w 3.0 Pharmacokinetic summary (Merck) 1.45 BIC monograph (Gilead, Canada) Compound type Monoprotic base Pharmacokinetic summary (Merck) Monoprotic acid EMA Summary, Biktarvy pK a 9.47 Pharmacokinetic summary (Merck) 8.60 BIC monograph (Gilead, Canada) Dose (mg) 100 Pharmacokinetic summary (Merck) 50 Pharmacokinetic summary (Gilead) Absorption Absorption model First order First order P eff man (×10 −4 cm/s) 3.11 Pharmacokinetic summary (Merck) 2.41 Predicted via SimCyp P app, Caco-2 (×10 −6 cm/s) 25 Pharmacokinetic summary (Merck) 14.8 Pharmacokinetic summary (Gilead) f a 0.66 Pharmacokinetic summary (Merck) 1.0 Pharmacokinetic summary (Gilead) k a (h −1 ) 1.36 Pharmacokinetic summary (Merck) 2.54 BIC population PK report Lag time (h) 0.20 Measured 0.24 Measured fu gut 1.0 Predicted via SimCyp 1.0 Predicted via SimCyp Distribution Distribution Model Full PBPK model Full PBPK model V ss / F (L/Kg) 0.61 Pharmacokinetic summary (Merck) 0.20 Pharmacokinetic summary (Gilead) f u 0.24 Pharmacokinetic summary (Merck) 0.25 Pharmacokinetic summary (Gilead) B:P 1.0 Pharmacokinetic summary (Merck) 0.64 Pharmacokinetic summary (Gilead) Elimination Elimination model Enzyme kinetics Enzyme kinetics CL renal (L/h) 0.57 Pharmacokinetic summary (Merck) 0.35 Predicted via SimCyp CYP3A4 Cl int (μL/min/pmol) 0.03 Pharmacokinetic summary (Merck) 0.05 Predicted via SimCyp Open in a separate window Abbreviations: BIC, bictegravir; B:P, blood-to-plasma partition ratio; CL renal , intrinsic renal clearance and the lag time for bictegravir and doravirine; f a , fraction of drug absorbed; f u , fraction of drug unbound in plasma; fu gut , fraction of drug unbound in gut enterocytes; k a , first-order absorption rate constant; log-P o:w , log of the octanol–water partition coefficient for the neutral compound; MW, molecular weight; P app, Caco-2 , apparent permeability coefficient in CACO-2 cells; P eff,man , intestinal effective permeability in humans; pKa, dissociation constant; V ss / F , volume of distribution at steady state.

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