Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic Function

Veronese, L.; Rautaureau, Jacques; Sadler, Brian M.; Gillotin, Catherine; Petite, J P; Pillegand, B; Delvaux, Michel; Masliah, Claude; Fosse, S.; Lou, Yu; Stein, Daniel S.

doi:10.1128/aac.44.4.821-826.2000

Cited by 68 publications

(40 citation statements)

References 13 publications

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“…44,45 Liver dysfunction may impair drug metabolism, which may enhance pharmacokinetic interactions between NNRTIs and PIs and increase the risk of hepatotoxicity by increasing drug concentrations. 30,34,[46][47][48][49] We were unable to investigate this hypothesis because liver histology and serum drug levels were unavailable in most patients.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections

et al. 2002

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Hepatologists are frequently asked to evaluate human immunodeficiency virus (HIV)-infected patients with abnormal liver enzymes and to assess the causal role of medications, such as antiretroviral drugs. Recently, the use of HIV-1 specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine (NVP) and efavirenz (EFV), has been associated with severe hepatic injury. We prospectively studied the incidence of severe hepatotoxicity (grade 3 or 4 change in alanine or aspartate transaminase levels) among 568 patients receiving NNRTI-containing antiretroviral therapy, including 312 and 256 patients prescribed EFV and NVP, respectively. Hepatitis C virus (HCV) and hepatitis B virus (HBV) were detected in 43% and 7.7% of patients, respectively. Severe hepatotoxicity was observed in 15.6% of patients prescribed NVP and 8.0% of those prescribed EFV, but only 32% of NVP and 50% of EFV-associated episodes were detected during the first 12-weeks of therapy. The risk was significantly greater among persons with chronic viral hepatitis (69% of cases) and those prescribed concurrent protease inhibitors (PIs) (82% of cases). Nonetheless, 84% of patients with chronic HCV or HBV did not experience severe hepatotoxicity. Severe hepatotoxicity occurs throughout the course of NNRTI therapy and is more common among patients prescribed nevirapine, those coinfected with HCV or HBV, and those coadministered protease inhibitors. (HEPATOLOGY 2002;35:182-189.)

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Section: Discussionmentioning

confidence: 99%

Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections

et al. 2002

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“…This interplay between HIV and HCV sets the tone for the objective of this study which is to ascertain the seroprevalence of HCV among newly diagnosed HIV patients in Ughelli, a suburban area of Delta State, Nigeria. This would help in the clinical management of the HIV-HCV co-infected patients especially in the choice and administration of highly active antiretroviral therapy (HAART) and will reduce the high incidence of drug-induced hepatoxicity commonly found among HIV-HCV patients which reported in several journals 23,24,25,26 .…”

Section: Introductionmentioning

confidence: 99%

Anti-HCV antibody among newly diagnosed HIV patients in Ughelli, a suburban area of Delta State Nigeria

O¹,

Oghene²,

Okonko³

2015

Afr H. Sci.

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Background: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share common routes of infection and as such, co-infection is expected. Co-infection of the two viruses is of great medical importance as it determines the effect of drugs used for treatment at various stages. Objective: This interplay between HIV and HCV sets the tone for the objective of this study which is to ascertain the seroprevalence of HCV among newly diagnosed HIV patients in Ughelli, a suburban area of Delta State, Nigeria. Methods: A total of 200 newly diagnosed HIV-positive patients were recruited for this study. Each of the sera was tested for anti-HCV antibody using SWE-life HCV ultra rapid test strip. Appropriate questionnaires were used to ascertain other important information which include social behaviour such as whether the patients were MSM (males), IDU, tattoo and/or have received blood transfusion in the past. Results: The prevalence of HCV among the study population was determined to be 15.0%. A higher seroprevalence was observed among females (16.5%) than in males (13.0%). A higher seroprevalence was also observed among age groups >26 years (16.0%) than in age-groups 14-25 years (13.0%) and 2-13 years (0.0%). Of the 7 patients with tattoos, 1(14.3%) tested positive for HCV compared to 29(15.0%) with no tattoos. We found no significant correlation with transfusion, intravenous drug use (IDU), men that have sex with men (MSM), tattooing and the seroprevalence of HCV. However, significant correlation existed with age, sex and HCV prevalence. Conclusion: This study reports a 15.0% seroprevalence of HCV among newly diagnosed HIV patients and that is alarmingly well above several other studies done in the past in Nigeria and other countries of sub-Saharan Africa. Planned prevention, screening, and treatment are needed to reduce further transmission and morbidity. Future studies involving HCV-RNA assays are needed.

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“…As the liver damage progresses, the metabolizing capabilities of members of the cytochrome P450 enzyme family decrease (2) and increased concentrations of antiretrovirals are likely to be found in plasma (27).…”

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Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

Regazzi¹,

Maserati

Villani³

et al. 2005

Antimicrob Agents Chemother

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In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV؉) patients coinfected with HCV. A total of 119 HIV؉ subjects were included in our study: 67 HIV؉ patients, 32 HIV؉ and HCV-positive (HCV؉) patients without cirrhosis, and 20 HIV؉ and HCV؉ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV؉ and HCV؉ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV؉ and HCV-negative individuals (28 and 58% lower, respectively; P < 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (P < 0.05) in HIV؉ and HCV؉ subjects with cirrhosis (0.06 ؎ 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV؉ and HCV-negative patients (0.16 ؎ 0.13) and HIV؉ and HCV؉ patients without cirrhosis (0.24 ؎ 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV؉ and HCV؉ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.

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Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic Function

Cited by 68 publications

References 13 publications

Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections

Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections

Anti-HCV antibody among newly diagnosed HIV patients in Ughelli, a suburban area of Delta State Nigeria

Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

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