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CYP2D6 is the major enzyme involved in the metabolism of venlafaxine. Subjects with a low CYP2D6 activity have increased plasma concentrations of venlafaxine that may predispose them to cardiovascular side effects. In vitro and in vivo studies showed that diphenhydramine, a nonprescription antihistamine, can inhibit CYP2D6 activity. Therefore, the authors(More)
Occurrence of a lupus-like syndrome in a significant number of patients treated with procainamide has limited the clinical use of this antiarrhythmic drug. In-vitro studies conducted in our laboratory have demonstrated that CYP2D6 is the major cytochrome P450 isozyme involved in the formation of N-hydroxyprocainamide, a metabolite potentially involved in(More)
The present population pharmacokinetic (PK) and pharmacodynamic (PD) study modeled the effects of covariates including drug adherence and the coadministration of protease inhibitors (PIs) on the pharmacokinetics of efavirenz (EFV) and the relationship between EFV exposure and virological failure in patients who failed initial PI treatment in Adult AIDS(More)
BACKGROUND Efavirenz and nelfinavir are metabolized by cytochrome P-450 (CYP) 2B6 and CYP2C19, respectively, with some involvement by CYP3A. Nelfinavir is a substrate for P-glycoprotein, which is encoded by MDR1. The present study examined associations between genetic variants and long-term responses to treatment. METHODS Adult AIDS Clinical Trials Group(More)
OBJECTIVE To develop and validate limited sampling strategies (LSSs) for tacrolimus in pediatric liver transplant recipients. METHODS Thirty-six 12-hour pharmacokinetic profiles from 28 pediatric liver transplant recipients (0.4-18.5 years) were collected. Tacrolimus concentrations were measured by immunoassay and area under the curve (AUC0-12) was(More)
The angiotensin-converting enzyme (ACE) gene is a candidate genetic locus for coronary artery disease (CAD). Studies investigating the relationship between the ACE-insertion/deletion (I/D) gene polymorphism and myocardial infarction (MI) have been inconsistent. The authors hypothesized that age may be an important modulating factor in this relationship.(More)
OBJECTIVE Pharmacokinetic interactions are expected when human immunodeficiency virus (HIV) protease inhibitors are coadministered because many are both substrates for and inhibitors of CYP3A4. The goal of this model-based pharmacokinetic analysis was to describe the differences observed in amprenavir pharmacokinetics among treatment arms in the Adult AIDS(More)
The effects of gender, time variables, menstrual cycle phases, plasma sex hormone concentrations and physiologic urinary pH on CYP2D6 phenotyping were studied using two widely employed CYP2D6 probe drugs, namely dextromethorphan and metoprolol. Phenotyping on a single occasion of 150 young, healthy, drug-free women and men revealed that the(More)
OBJECTIVE For the HIV-1 reverse transcriptase inhibitor efavirenz, variant drug transporter gene ABCB1 may predict virologic response but not plasma efavirenz exposure. Conversely, variant drug metabolizing enzyme gene CYP2B6 predicts greater plasma efavirenz exposure but not virologic response. We examined whether long-term responses to efavirenz, and/or(More)
Population pharmacokinetics has been an important technique used to explore and define relevant sources of variation in drug exposure and response in patient populations. This has been especially true in the area of antiretroviral therapy where the assurance of adequate and sustained drug exposure of multiple agents is highly correlated with therapeutic(More)