Raltegravir is primarily cleared by hepatic metabolism via glucuronidation (via UDP glucuronosyltransferase 1A1), with a minor component of elimination occurring via the renal pathway.
Since the potential exists for raltegravir to be administered to patients with hepatic or renal insufficiency, two studies were conducted to evaluate the influence of moderate hepatic insufficiency (assessed by using the Child-Pugh criteria) and severe renal insufficiency (creatinine clearance, <30 ml/min/1.73 m(2)) on the pharmacokinetics of raltegravir.
Study I evaluated the pharmacokinetics of 400 mg raltegravir in eight patients with moderate hepatic insufficiency and eight healthy, matched control subjects.
Study II evaluated the pharmacokinetics of 400 mg raltegravir in 10 patients with severe renal insufficiency and 10 healthy, matched control subjects.
All participants received a single 400-mg dose of raltegravir in the fasted state.
In study I, the geometric mean ratios (GMR; mean value for the group with moderate hepatic insufficiency/mean value for the healthy controls) and 90% confidence intervals (CIs) for the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)), the maximum concentration of drug in plasma (C(max)), and the concentration at 12 h (C(12)) were 0.86 (90% CI, 0.41, 1.77), 0.63 (90% CI, 0.23, 1.70), and 1.26 (90% CI, 0.65, 2.43), respectively.
In study II, the GMRs (mean value for the group with renal insufficiency/mean value for the healthy controls) and 90% CIs for AUC(0-infinity), C(max), and C(12) were 0.85 (90% CI, 0.49, 1.49), 0.68 (90% CI, 0.35, 1.32), and 1.28 (90% CI, 0.79, 2.06), respectively.
Raltegravir was generally well tolerated by patients with moderate hepatic or severe renal insufficiency, and there was no clinically important effect of moderate hepatic or severe renal insufficiency on the pharmacokinetics of raltegravir.
No adjustment in the dose of raltegravir is required for patients with mild or moderate hepatic or renal insufficiency.
- DOI - Antimicrobial agents and chemotherapy (DOI)
- EBSCO - full-text online (subscription/membership/fee required)
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JournalAntimicrobial agents and chemotherapy
Antimicrob Agents Chemother (1098-6596)
Antimicrobial agents and chemotherapy
Merck & Co., Inc., Whitehouse Station, New Jersey, USA. marian_iwamoto [at] merck.com
Antimicrob Agents Chemother. 2009 May;53(5):1747-52
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