Pharmacokinetics of emtricitabine/tenofovir disoproxil fumarate and tacrolimus at steady state when administered alone or in combination.
OBJECTIVE
An open-label, randomized, 3-way crossover, drug-drug interaction study of the investigational anti-HBV combination agent, emtricitabine/tenofovir DF and the antirejection agent, tacrolimus was conducted in healthy volunteers to evaluate the potential for a pharmacokinetic interaction between these drugs.


METHODS
Subjects received emtricitabine/tenofovir DF (200/300 mg q.d.) and tacrolimus (0.1 mg/kg/day) alone or in combination for 7 days, with a 2-week washout between successive treatments. Drug concentrations were measured by LC/MS/MS and steady state pharmacokinetic parameters were calculated for each drug using noncompartmental methods.


RESULTS
The 90% confidence intervals (CIs) of the geometric least-squares mean ratio for AUCtau, Cmax and Ctau for each drug together vs. alone were within the predetermined no-effect boundaries of 80 - 125% (representing a maximum 20% effect), other than the upper limit of the 90% CI for tenofovir Cmax, which was just outside the 125% threshold.


CONCLUSIONS
It was concluded that there was no clinically relevant pharmacokinetic interaction between emtricitabine/tenofovir DF and tacrolimus when administered together.
Chittick
G E
GE
Gilead Sciences, Inc., Durham, NC 27707, USA.
Zong
J
J
Begley
J A
JA
Alianti
J R
JR
Sorbel
J J
JJ
Blum
M R
MR
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000328:Adult; D019540:Area Under Curve; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000068679:Emtricitabine; D005260:Female; D005414:Flatulence / Q000139:chemically induced; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D063065:Organophosphonates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000068698:Tenofovir; D013997:Time Factors; D055815:Young Adult
D007166:Immunosuppressive Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D016559:Tacrolimus