关键词: CYP2C8 Cheng-Prusoff equation Drug-drug interaction Fraction unbound Free drug hypothesis Microsomal proteins Montelukast Protein binding

Mesh : Acetates / pharmacokinetics Area Under Curve Cyclopropanes / pharmacokinetics Cytochrome P-450 CYP2C8 / metabolism Drug Interactions Humans Kinetics Plasma / chemistry Quinolines / pharmacokinetics Rosiglitazone / administration & dosage pharmacokinetics Sulfides / pharmacokinetics

来  源:   DOI:10.1007/978-1-0716-1554-6_24

Abstract:
Predicting drug-drug interactions (DDIs) from in vitro data is made difficult by not knowing concentrations of substrate and inhibitor at the target site. For in vivo targets, this is understandable, since intracellular concentrations can differ from extracellular concentrations. More vexing is that the concentration of the drug at the target for some in vitro assays can also be unknown. This uncertainty has resulted in standard in vitro practices that cannot accurately predict human pharmacokinetics. This case study highlights the impact of drug distribution, both in vitro and in vivo, with the example of the drug interaction potential of montelukast.
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