title: Case study 4. Predicting the drug interaction potential for inhibition of CYP2C8 by montelukast.
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.
authors: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
authors: Ken
authors: K
authors: Korzekwa
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D003521:Cyclopropanes; D065727:Cytochrome P-450 CYP2C8; D004347:Drug Interactions; D057075:Enzyme Assays / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D042541:Intracellular Space / Q000201:enzymology; D011804:Quinolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077154:Rosiglitazone; D013440:Sulfides; D045162:Thiazolidinediones / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D011804:Quinolines; D013440:Sulfides; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; C093875:montelukast