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Maraviroc Levels Up One Third in People With Liver Impairment
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8th International Workshop on Pharmacology of HIV Therapy
April 16-18, 2007, Budapest
Mark Mascolini
Concentrations of the CCR5 antagonist maraviroc stood one third to nearly one half higher in people with moderate liver impairment than in people with normal liver function, according to a study Pfizer presented at the HIV Pharmacology Workshop [1]. Oral clearance of the drug decreased as hepatic impairment worsened.
In a nonblinded study Pfizer researchers measured maraviroc levels for 72 hours after a single 300-mg dose in three groups: 8 people with mild liver impairment (Child-Pugh class A), 8 with moderate impairment (Child-Pugh class B), and 8 with no impairment. The people with healthy livers were matched to those with mild or moderate impairment for age (plus or minus 5 years), weight (plus or minus 10 kg), and gender. Everyone fasted at least 8 hours before taking maraviroc and at least 4 hours afterwards.
Average maraviroc maximum concentration (Cmax) proved substantially higher in people with moderate liver impairment (534 ng/mL) than in those with mild impairment (436 ng/mL) or no impairment (410 ng/mL). Maraviroc's average last area under the concentration-time curve (AUClast) was also higher with moderate liver impairment (2621 ng/hour/mL) than with mild impairment (2144 ng/hour/mL) or no impairment (1815 ng/hour/mL).
Geometric mean ratio (and 90% confidence intervals) for maraviroc Cmax in people with moderate impairment versus no impairment measured 132% (89.6% to 194%). For maraviroc AUClast, the geometric mean ratio for those two groups stood at 146% (100% to 212%). In other words Cmax was 32% higher and AUClast 46% higher with moderate impairment than with no impairment. For people with mild liver impairment versus no impairment, geometric mean ratios were 111% (74.6% to 166%) for Cmax and 125% (84.7% to 185%) for AUClast.
Oral clearance of maraviroc measured 153 L/hour for people with a healthy liver, 149 L/hour for those with mild impairment, and 129 L/hour for those with moderate impairment. Maraviroc half-life and time to maximum concentration did not differ in the three study groups.
Side effects in this single-dose study were rare and mild.
The Pfizer team did not suggest whether a maraviroc dose adjustment will be needed for people with mild or moderate liver impairment.
Reference
1. Abel S, Ridgway C, Hamlin J, Davis J. An open, parallel group study to compare the pharmacokinetics, safety and toleration of a single oral dose of maraviroc in subjects with mild and moderate hepatic impairment with subjects with normal hepatic function. 8th International Workshop on Pharmacology of HIV Therapy. April 16-18, 2007. Budapest. Abstract 8.
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