Steady-state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate administered alone and in combination in healthy volunteers.
The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, were considered good candidates for a fixed-dose combination product that could be administered as a single pill once daily (qd), thereby simplifying existing treatment regimens and promoting patient adherence. As both drugs are extensively renally eliminated, a randomized, 3-way crossover study was conducted in 19 healthy volunteers to formally evaluate the potential pharmacokinetic interaction when the drugs are administered alone and together (ie, 200 mg emtricitabine qd for 7 days, 300 mg tenofovir disoproxil fumarate qd for 7 days, and 200 mg emtricitabine plus 300 mg tenofovir disoproxil fumarate qd for 7 days) with no washout between treatments. Steady-state pharmacokinetic parameters (AUC(tau), C(max), and C(min)) of emtricitabine and tenofovir (as tenofovir disoproxil fumarate) in combination were essentially equivalent versus each drug alone, providing a pharmacokinetic rationale for combining these products in emtricitabine/tenofovir disoproxil fumarate fixed-dose tablets.
Blum
M Robert
MR
Gilead Sciences, Inc, 4 University Place, 4611 University Drive, Durham, NC 27709, USA. robert.blum@gilead.com
Chittick
Gregory E
GE
Begley
John A
JA
Zong
Jian
J
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068698:Tenofovir
D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine