Conditions: Efavirenz, Metabolism and Pharmacokinetics Changes
Keywords: Cytochrome P450 CYP2B6 Voriconazole Efavirenz Pharmacokinetics Drug-Interactions Pharmacogenetics Healthy volunteers
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 61
Healthy volunteers: yes

Brief summary:
The purpose of this study is to see if administration of medicines and genetic differences affects the activity of a liver enzyme called CYP2B6 in healthy volunteers.

Detailed description:
The investigators will test the hypothesis that CYP2B6 genetic variants that show effects in vitro also influence the in vivo activity of CYP2B6 and its responsiveness to metabolic inhibition, using the metabolism of efavirenz (100 mg dose) as a marker of activity. The metabolism and pharmacokinetics of efavirenz will be determined in a total of 60 healthy volunteers with CYP2B6\*1/\*1, CYP2B6\*1\*6 and CYP2B6\*6\*6 at baseline (control) and after pretreatment with voriconazole.

Arms:
arm 1: Healthy volunteers will receive Efavirenz and Vericonazole as follow:

In phase 1 day 1 (control phase) a single 100mg dose of efavirenz will be administered. In phase 2 (voriconazole pretreatment phase), the subject will be pretreated with voriconazole (400mg twice daily on phase 2 day 8 and then 200mg twice daily for the next consecutive 8 days. In phase 3 (efavirenz plus voriconazole phase), the subject will receive on phase 3 day 10 100mg single dose of efavirenz along with 200mg of voriconazole twice daily.

Interventions: intervention 1: Efavirenz intervention 2: voriconazole
Intervention descriptions: intervention 1: In phase 1 day 1 (control phase) a single 100mg dose of efavirenz will be administered.

In phase 2 (voriconazole pretreatment phase), the subject will be pretreated with voriconazole (400mg twice daily on phase 2 day 8 and then 200mg twice daily for the next consecutive 8 days. In phase 3 (efavirenz plus voriconazole phase), the subject will receive on phase 3 day 10 100mg single dose of efavirenz along with 200mg of voriconazole twice daily. intervention 2: In phase 1 day 1 (control phase) a single 100mg dose of efavirenz will be administered.

In phase 2 (voriconazole pretreatment phase), the subject will be pretreated with voriconazole (400mg twice daily on phase 2 day 8 and then 200mg twice daily for the next consecutive 8 days. In phase 3 (efavirenz plus voriconazole phase), the subject will receive on phase 3 day 10 100mg single dose of efavirenz along with 200mg of voriconazole twice daily.

Protocol document: