Tenofovir comedication does not impair the steady-state pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected adults.
OBJECTIVE
Our objective was to evaluate the steady-state pharmacokinetics of ritonavir-boosted atazanavir when coadministered with tenofovir in HIV-1-infected adult patients.


METHODS
Forty adult HIV-1-infected patients received either atazanavir/ritonavir 300/100 mg once daily and nucleoside reverse transcriptase inhibitors with (n = 20) or without (n = 20) tenofovir-disoproxil fumarate (tenofovir-DF) 300 mg once daily. Twenty-four-hour pharmacokinetics were assessed after at least 2 weeks of therapy according to a standardised therapeutic drug monitoring protocol.


METHODS
Atazanavir/ritonavir plasma concentrations were measured by liquid chromatography tandem mass spectrometry, and the geometric means of minimum and maximum concentrations (C(min), C(max)), the area under the time-concentration curve (AUC), half-life (t(1/2)) and total clearance (CL(tot)) were subject to a matched pairs-analysis. Patients' pairs were matched for gender, ethnicity, weight and Center for Disease Control and Prevention (CDC) status.


RESULTS
The respective geometric means (90% CI) for atazanavir C(min), C(max) and AUC with tenfovir vs. without tenofovir were 405 (314-523) vs. 417 (304-572) ng/ml, 3,022 (2,493-3,664) vs. 2,817 (2,341-3,390) ng/ml and 34,822 (29,315-41,363) vs. 32,101 (26,206-39,321) ng x h/ml showing no significant differences between the groups. Atazanavir plasma concentrations measured at week 5 of therapy or later were lower than in the first 4 weeks (T-test for C(max), p = .080; AUC, p = .050 and CL(tot), p = .051).


CONCLUSIONS
The coadministration of tenofovir-DF did not impair the plasma concentrations of ritonavir-boosted atazanavir in a pharmacokinetic analysis of patient pairs matched for gender, ethnicity, weight and CDC status.
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. Hentig@em.uni-frankfurt.de
Nils
N
von Hentig
Brenda
B
Dauer
Annette
A
Haberl
Stefan
S
Klauke
Thomas
T
Lutz
Schlomo
S
Staszewski
Sebastian
S
Harder
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D002853:Chromatography, Liquid; D004338:Drug Combinations; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008657:Metabolic Clearance Rate; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use*; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir