Abacavir plasma pharmacokinetics in the absence and presence of atazanavir/ritonavir or lopinavir/ritonavir and vice versa in HIV-infected patients.
BACKGROUND
Significant interactions between abacavir and other antiretrovirals have not been reported. This study investigated the steady-state plasma pharmacokinetics of abacavir when co-administered with atazanavir/ritonavir or lopinavir/ritonavir in HIV-infected individuals.


METHODS
HIV-infected subjects on abacavir (600 mg once daily) plus two nucleoside reverse transcriptase inhibitors (NRTIs) (excluding tenofovir) underwent a 24 h pharmacokinetic assessment for plasma abacavir concentrations. Atazanavir/ritonavir (300/100 mg once daily; arm (1) or lopinavir/ritonavir (400/100 mg twice daily; arm (2) were then added and the 24 h pharmacokinetic assessment repeated. Arm 3 included subjects stable on atazanavir/ritonavir or lopinavir/ritonavir and two NRTIs (excluding tenofovir or abacavir). These patients underwent a pharmacokinetic assessment for atazanavir/ritonavir or lopinavir/ritonavir concentrations on day 1, abacavir (600 mg once daily) was then added to the regimen and the pharmacokinetic assessment repeated. Within-subject changes in drug exposure were evaluated by geometric mean (GM) ratios and 95% confidence intervals (CI).


RESULTS
Twenty-four patients completed the study. GM (95% CI) abacavir area under the curve (AUC) was 18,621 (15,900-21,807) and 15,136 (13,339-17,174) ng.h/ml without and with atazanavir/ritonavir and 15,136 (12,298-18,628) and 10,471 (9,270-11,828) ng.h/ml without and with lopinavir/ritonavir. GM (95% CI) atazanavir AUC without and with abacavir was 26,915 (13,252-54,666) and 28,840 (19,213-43,291) ng.h/ml; lopinavir AUC without and with abacavir was 60,253 (48,084-75,509) and 63,096 (48,128-82,718) ng.h/ml.


CONCLUSIONS
No changes in atazanavir or lopinavir exposures were observed following the addition of abacavir; however, decreases in abacavir plasma exposure of 17% and 32% were observed following the addition of atazanavir/ritonavir or lopinavir/ritonavir, respectively.
Waters
Lauro J
LJ
St. Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
Moyle
Graeme
G
Bonora
Stefano
S
D'Avolio
Antonio
A
Else
Laura
L
Mandalia
Sundhiya
S
Pozniak
Anton
A
Nelson
Mark
M
Gazzard
Brian
B
Back
David
D
Boffito
Marta
M
D000328:Adult; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000099227:Abacavir
D000069446:Atazanavir Sulfate; D015224:Dideoxynucleosides; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D000099227:Abacavir