Pharmacokinetics of coadministered ritonavir-boosted elvitegravir and zidovudine, didanosine, stavudine, or abacavir.
OBJECTIVE
To evaluate the potential for clinically relevant drug interactions between ritonavir-boosted elvitegravir (EVG/r) and the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine (ZDV), didanosine (ddI), stavudine (d4T), or abacavir (ABC) upon coadministration.


METHODS
In 3 studies, healthy subjects were administered a single dose of ddI, d4T, or ABC, or multiple doses of ZDV, followed by multiple doses of EVG/r alone and together with an NRTI; pharmacokinetics (PK) of EVG and NRTIs were evaluated after individual administration and coadministration. Lack of PK alteration bounds (90% confidence intervals [CI]) for the NRTIs were based on the lack of PK-based dose adjustments per prescribing information.


RESULTS
Twenty-four of 28, 32/32, and 24/26 subjects completed the ZDV-EVG/r, ddI/d4T-EVG/r, and ABC-EVG/r studies, respectively. All study drugs were well tolerated and no serious adverse events were noted. The PK of ZDV, its glucuronide (G-ZDV), d4T, ABC, and EVG were within the lack of PK alteration 90% CI bounds upon coadministration. Exposures of ddI were modestly (approximately 15%) lower, but these changes are unlikely to be clinically meaningful.


CONCLUSIONS
There are no clinically relevant drug interactions between EVG/r and the NRTIs zidovudine, didanosine, stavudine, or abacavir. These agents can be coadministered without dose adjustment.
Ramanathan
Srinivasan
S
Gilead Sciences, Foster City, CA 94404, USA. sramanathan@gilead.com
Shen
Gong
G
Hinkle
John
J
Enejosa
Jeffrey
J
Kearney
Brian P
BP
D000293:Adolescent; D000328:Adult; D016001:Confidence Intervals; D018592:Cross-Over Studies; D016049:Didanosine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018119:Stavudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000099227:Abacavir
D016049:Didanosine; D015224:Dideoxynucleosides; D015363:Quinolones; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir; C509700:elvitegravir