Raltegravir and darunavir pharmacokinetics in liver disease
The pharmacokinetic profiles of darunavir and raltegravir were analysed in five HIV/HCV coinfected patients with moderate to severe liver disease. Based on the ultrasonographic and histological evaluation, two patients had HCV-related chronic active hepatitis, and three patients had a diagnosis of cirrhosis (Child Pugh stage B). Trough concentrations were determined 14 and 30 days after starting a raltegravir/darunavir containing regimen.
Mean raltegravir and darunavir trough concentrations in the hepatic impairment group was 637 (mean Ctrough in control group: 221±217 ng/ml) and 8519 ng/mL (mean Ctrough in control group: 3236±2183 ng/ml), respectively. In a sub-group analysis, patients with cirrhosis had higher mean raltegravir Ctrough than patients with active non cirrhotic hepatitis (665 vs 581 ng/mL). The mean darunavir Ctrough was consistently higher in cirrhotic than non cirrhotic patients (9820 vs 2016 ng/mL).
The data suggest special caution in the use of raltegravir, and especially of darunavir, in patients with moderate to severe liver impairment because of the risk of additionally increased toxicity.
Ref: Tommasi C et al. Raltegravir and darunavir plasma pharmacokinetic in HIV-1 infected patients with advanced liver disease.11th PK Workshop, 2010. Abstract 10.