Pharmacokinetics of emtricitabine, tenofovir, and GS-9137 following coadministration of emtricitabine/tenofovir disoproxil fumarate and ritonavir-boosted GS-9137.
OBJECTIVE
To evaluate the potential for clinically relevant drug-drug interaction between emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and the ritonavir-boosted HIV integrase inhibitor GS-9137 (GS-9137/r).


METHODS
Healthy adults were administered FTC/TDF (200/300 mg once daily) for 7 days, followed by randomization to the order of receiving GS-9137/r (50/100 mg once daily) and GS-9137/r plus FTC/TDF in a crossover fashion under fed conditions for 10 days. Pharmacokinetic (PK) blood draws were performed on days 7, 17, and 27. Lack of PK alteration for FTC, tenofovir (TFV), and GS-9137 was defined as a 90% confidence interval (CI) for the estimated ratio of geometric least squares means (coadministration/alone) between 70% and 143% for the primary PK parameters: maximum observed plasma concentration (Cmax), area under the plasma concentration-time curve over dosing interval (AUCtau), and trough concentration (Ctau).


RESULTS
Twenty-four of the 26 enrolled subjects completed the study with no serious adverse events or discontinuations attributable to adverse events. FTC, TFV, and GS-9137 PKs were unaffected during coadministration, with Cmax, AUCtau, and Ctau, meeting the protocol definition of equivalence and also the stricter bioequivalence criteria (90% CI: 80% to 125%). FTC and TFV PK parameters were comparable to historical values.


CONCLUSIONS
There is no clinically relevant drug-drug interaction between FTC/TDF and GS-9137/r on their coadministration.
Ramanathan
Srinivasan
S
Gilead Sciences, Inc., Foster City, CA 94404, USA. sramanathan@gilead.com
Shen
Gong
G
Cheng
Andrew
A
Kearney
Brian P
BP
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068698:Tenofovir
D000998:Antiviral Agents; D063065:Organophosphonates; D015363:Quinolones; D003841:Deoxycytidine; C509700:elvitegravir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir