Pharmacokinetic effects of coadministration of lersivirine with raltegravir or maraviroc in healthy subjects.
Vourvahis M, Langdon G, Labadie RR, et al.
Antimicrob Agents Chemother, 2012, 56(2): 887-892.

Lersivirine is a new NNRTI which is metabolized by glucuronidation (UGT2B7) and CYP3A4. As it is also a weak inducer of CYP3A4, coadministration could potentially affect the pharmacokinetics of maraviroc (a CYP3A4 substrate) and raltegravir (metabolized by glucuronidation).

 
Two open-label studies in healthy subjects assessed the pharmacokinetics of raltegravir (400 mg twice daily, n=18) with lersivirine (1000 mg once daily), or maraviroc (300 mg twice daily, n=14) with lersivirine (500 mg twice daily).  Coadministration decreased raltegravir AUC, Cmax and C12h by 15%, 29% and 25%, respectively, but these effects were regarded as not being clinically significant. There were no clinically relevant effects of raltegravir on lersivirine AUC, Cmax or C24h (estimated mean changes of −2 to +5%). In the presence of lersivirine, no clinically significant changes in maraviroc pharmacokinetics were observed: AUC, Cmax and C12h increased by 6%, 3% and 9%, respectively.

 
Lersivirine appeared to be generally well tolerated in these studies and appears to be suitable for coadministration with raltegravir or maraviroc without the need for dose modification.