Maraviroc + Tipranavir = Precautionary

Study Design

The design of this study was an open label, randomized, placebo-controlled study done in health subjects, to assess the effect of CYP3A4 inhibitor combinations on the pharmacokinetics of the CCR5 antagonist maraviroc. (n=12) healthy men and women aged 22-43 were enrolled in a two-way cross over study to investigate the influence of ritonavir boosted tipranavir (TPV/r) on the plasma pharmacokinetics of maraviroc. Subjects received 150mg of maraviroc BID while subsequently receiving 500/200mg of TPV/r or placebo BID on treatment days 1-7 with the final dose of maraviroc given on day 8. Subjects during this study fasted overnight until 1 hour post maraviroc dose on days 1-7, and 4 hours post maraviroc dose on day 8. The two treatment periods were separated by a wash-out period of at least 14 days, with subjects returning for follow up within 7-10 days after the final dose. Serial blood samples were collected predose on day s1-8 and at intervals up to 12h post dose on day 8. Urine samples were collected from 0-12h post dose on day 8. Geometric least squares ratios and 90% confidence intervals were estimated. Based on GMRs and 90% confidence intervals, when compared with maraviroc + placebo there was a 102% increase in AUC (85, 123) and a 86% increase in Cmax (61, 121) of maraviroc upon co-administration with the boosted protease inhibitor TPV/r. This combination was generally well tolerated, with no adverse events leading to treatment discontinuation.

Study Results

Per the authors, clinically significant alterations in maraviroc exposure can be attributed to the co-administration with HIV protease inhibitors (or other modulators of CYP3A4 activity). However dosage adjustments can compensate for the PK alterations.1

Study Conclusions

References

Abel S, Russell D, Taylor-Worth RJ, Ridgway CE, Muirhead GJ. Effects of cyp3a4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. British Journal Of Clinical Pharmacology. 2008; S1: 27-37.