The anticancer alkylating agents cyclophosphamide (CPA) and ifosfamide (IFA) are prodrugs that undergo extensive P450-catalyzed metabolism to yield both active (4-hydroxylated) and therapeutically inactive but neurotoxic (N-dechloroethylated) metabolites. Whereas the human liver microsomal P450 catalysts of CPA and IFA 4-hydroxylation are well characterized, the P450 enzyme catalysts of the alt...

AIMS To assess the cost-effectiveness of CYP2B6 genotyping to guide efavirenz dosing for initial HIV therapy in the USA. METHODS We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) microsimulation model to project quality-adjusted life expectancy and lifetime costs (2014 US dollars) for efavirenz-based HIV therapy with or without CYP2B6 genotyping. We assumed that with gen...

Ketamine is metabolized by cytochrome P450 (CYP) leading to production of pharmacologically active products and contributing to drug excretion. We identified the CYP enzymes involved in the N-demethylation of ketamine enantiomers using pooled human liver microsomes and microsomes from human B-lymphoblastoid cells that expressed CYP enzymes. The kinetic data in human liver microsomes for the (R)...

  Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavi...

Cytochrome P450 2B6 (CYP2B6) metabolizes clinically important drugs and other compounds. Its expression and activity vary widely among individuals, but quantitative estimation is hampered by the lack of safe and selective in vivo probes of CYP2B6 activity. Efavirenz, a nonnucleoside HIV-1 reverse transcriptase inhibitor, is mainly cleared by CYP2B6, an enzyme strongly inhibited in vitro by vori...

UNLABELLED This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time...

Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonl...

Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in human immunodeficiency virus (HIV) treatment can cause hypersensitivity reactions in 6-10% of patients, which in the most serious cases (1.3%) can manifest as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN). A total of 209 patients with NVP hypersensitivity (57 from a prospective cohort and 152...

Since antiretroviral drugs are known to inhibit many cytochrome P450 isoforms, the inhibition of CYP2B6 by non-nucleoside reverse transcriptase inhibitors and viral protease inhibitors was studied in vitro in human liver microsomes using bupropion hydroxylation as the CYP2B6 index reaction. Mean IC(50) values (microM) for inhibition of bupropion hydroxylation were: nelfinavir (2.5), ritonavir (...

BACKGROUND Polymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outco...