Antiretroviral drug pharmacokinetics in hepatitis with hepatic dysfunction.
Chronic viral hepatitis is common among persons with HIV-1 infection, because of shared modes of transmission, and coinfection results in accelerated liver damage, compared with persons with chronic viral hepatitis alone. The use of highly active antiretroviral therapy (HAART) has led to a significant decrease in the morbidity and mortality associated with HIV-1 infection. A number of the medications that are commonly used in HAART regimens are metabolized by the hepatic CYP enzymes, which raises the possibility of significant interactions between antiretroviral medications and hepatic impairment induced by chronic viral hepatitis. Although the data are still very scant, the pharmacokinetics of several antiretroviral medications have been shown to be significantly altered in the presence of liver disease. In the present report, we review the available data and consider potential options, such as dose adjustment and therapeutic drug monitoring, for the administration of antiretroviral therapy to patients with significant hepatic impairment.
Wyles
David L
DL
Department of Medicine, Divisions of Infectious Diseases and Clinical Pharmacology, University of Colorado Health Sciences Center, Denver, USA.
Gerber
John G
JG
D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000378:metabolism*; D006505:Hepatitis / Q000150:complications / Q000378:metabolism*; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics; D008111:Liver Function Tests; D061466:Lopinavir; D019888:Nelfinavir / Q000493:pharmacokinetics; D019829:Nevirapine / Q000493:pharmacokinetics; D010078:Oxazines / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000493:pharmacokinetics; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics; D019438:Ritonavir / Q000493:pharmacokinetics; D019258:Saquinavir / Q000493:pharmacokinetics; D015215:Zidovudine / Q000493:pharmacokinetics; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019469:Indinavir; D061466:Lopinavir; D019888:Nelfinavir; D019829:Nevirapine; D010078:Oxazines; D011480:Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D019258:Saquinavir; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz