Pharmacokinetic and Pharmacodynamic Analysis of Efavirenz Dose Reduction Using an In Vitro-In Vivo Extrapolation Model

The pharmacokinetics (PK) of efavirenz (EFV) is characterized by marked inter-patient variability that correlates with its pharmacodynamics (PD). In vitro-in vivo extrapolation (IVIVE) is a “bottom-up” approach that combines drug data with system information to predict PK and PD. The aim of this study was to simulate EFV PK and PD after dose reductions. At […]

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Application of a Systems Approach to the Bottom-up Assessment of Pharmacokinetics in Obese Patients: Expected Variations in Clearance

The maintenance dose of a drug is dependent on drug clearance, and thus any biochemical and physiological changes in obesity that affect parameters such as cardiac output, renal function, expression of drug-metabolizing enzymes and protein binding may result in altered clearance compared with that observed in normal-weight subjects (corrected or uncorrected for body weight). Because […]

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Towards a Quantitative Framework for the Prediction of DDIs Arising from Cytochrome P450 Induction

Although CYP induction is not generally considered to be as clinically relevant as CYP inhibition, there are important examples where induction has caused both therapeutic failure, due to insufficient exposure to parent drug, and toxicity, mediated by increased formation of reactive metabolites. Furthermore, while there has been considerable progress in the extrapolation of in vitro […]

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