Pharmacokinetics of lopinavir/ritonavir in HIV/hepatitis C virus-coinfected subjects with hepatic impairment.
The effect of hepatic impairment on lopinavir/ritonavir pharmacokinetics was investigated. Twenty-four HIV-1-infected subjects received lopinavir 400 mg/ritonavir 100 mg twice daily prior to and during the study: 6 each with mild or moderate hepatic impairment (and hepatitis C virus coinfected) and 12 with normal hepatic function. Mild and moderate hepatic impairment showed similar effects on lopinavir pharmacokinetics. When the 2 hepatic impairment groups were combined, lopinavir Cmax and AUC12 were increased 20% to 30% compared to the controls. Hepatic impairment increased unbound lopinavir AUC12 by 68% and Cmax by 56%. The effect of hepatic impairment on low-dose ritonavir pharmacokinetics was more pronounced in the moderate impairment group (181% and 221% increase in AUC12 and Cmax, respectively) than in the mild impairment group (39% and 61% increase in AUC12 and Cmax, respectively). While lopinavir/ritonavir dose reduction is not recommended in subjects with mild or moderate hepatic impairment, caution should be exercised in this population.
Abbott Laboratories, Clinical Pharmacology & Pharmacometrics (Department R4PK, Building AP13A-3), 100 Abbott Park Road, Abbott Park, IL 60064-6104, USA.
Joanna Z
JZ
Peng
Federico
F
Pulido
Sonja J Kemmis
SJ
Causemaker
Jianling
J
Li
Alicia
A
Lorenzo
Concepción
C
Cepeda
Juan A
JA
García Cabanillas
Barbara
B
DaSilva
Scott C
SC
Brun
José
J
Arribas
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D004338:Drug Combinations; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D015497:HIV-1; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D019438:Ritonavir / Q000493:pharmacokinetics*
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir