Pharmacokinetic interaction of ritonavir-boosted elvitegravir and maraviroc.
BACKGROUND
The pharmacokinetic (PK) interaction between ritonavir-boosted elvitegravir (elvitegravir/r) and maraviroc was evaluated.


METHODS
Healthy subjects were randomized to receive elvitegravir/r (150/100 mg once daily) before or after elvitegravir/r plus maraviroc (150 mg twice daily) (group 1; n = 20) or receive maraviroc before or after maraviroc plus elvitegravir/r (group 2; n = 16). All regimens were administered for 10 days and elvitegravir, ritonavir, and maraviroc PK determined. Lack of PK alteration was defined as 90% confidence intervals for ratio of geometric least squares means ratio (coadministration:alone) between 70% and 143% for elvitegravir and ritonavir Cmax (maximum concentration), Ctau (trough), and AUCtau (area under plasma concentration-time curve; 0-24 hours); for maraviroc, given a 100% increase in Cmax and AUCtau (0-12 hours); the predicted 90% confidence intervals were 162% to 247% and 136% to 295%, respectively.


RESULTS
Twenty-eight of 36 enrolled subjects completed the study; one discontinuation was due to an adverse event. The most common adverse event across treatments was headache. Upon coadministration, elvitegravir and ritonavir PK were unaltered, but maraviroc exposures were 2-fold to 4-fold higher presumably due to ritonavir-mediated CYP3A-/Pgp inhibition.


CONCLUSIONS
During elvitegravir/r plus maraviroc administration, no elvitegravir or ritonavir dose change and a reduced 150-mg dose of maraviroc are recommended.
Gilead Sciences, Inc, Foster City, CA 94404, USA. sramanathan@gilead.com
Srinivasan
S
Ramanathan
Samantha
S
Abel
Sarah
S
Tweedy
Steve
S
West
James
J
Hui
Brian P
BP
Kearney
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006207:Half-Life; D006801:Humans; D000077592:Maraviroc; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D019380:Anti-HIV Agents; D003510:Cyclohexanes; D015363:Quinolones; D014230:Triazoles; C509700:elvitegravir; D000077592:Maraviroc; D019438:Ritonavir