Interaction of CYP2B6 Genotype and Efavirenz Methadone and Tizanidine PK
Status:
Not yet recruiting
Trial end date:
2026-04-15
Target enrollment:
Participant gender:
Summary
The main goal of this clinical study is to test how CYP2B6 genetic variations and efavirenz
(cornerstone in HIV-1 therapy) dictate the disposition (PK) of CYP2B6 substrate (methadone)
and PK and effect (PD) of CYP1A2 substrate (tizanidine). Specifically, we will test whether
efavirenz produces CYP2B6 genotype dependent unanticipated DDIs with CYP2B6 (methadone) and
CYP1A2 (tizanidine), leading to lack of efficacy or increased toxicity. Healthy volunteers
genotyped for CYP2B6*6 and *18 alleles will be grouped in to three genotype predicted
phenotype groups: 20 normal metabolizer (NM) (CYP2B6*1/*1); 20 intermediate metabolizer (IM)
(*1/*6, or *1/*18); and 20 poor metabolizer (PM) (*6/*6, *6/*18 or *18/*18). Each phenotype
group will receive methadone and tizanidine (separated by a washout period) on two occasions:
at baseline (control) and after treatment with efavirenz (600 mg/day for 17 days).