| Title | Pharmacokinetic Interaction of Ritonavir-Boosted Elvitegravir and Maraviroc. | | Author(s) | Ramanathan S, Abel S, Tweedy S, West S, Hui J, Kearney BP | | Institution | From the *Gilead Sciences, Inc, Foster City, CA; daggerValley Writing Solutions Ltd, Barham, Kent, United Kingdom, double daggerPfizer Ltd, Sandwich, Kent, United Kingdom, and section signGilead Sciences, Inc, Durham, NC. Samantha Abel was formerly with Pfizer Ltd, Sandwich, Kent, United Kingdom. | | Source | J Acquir Immune Defic Syndr 2009 Oct 22. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19851115 |
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