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1: Clin Pharmacol Ther. 2008 Dec;84(6):698-703. Epub 2008 Jun 4.
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The effect of atazanavir and atazanavir/ritonavir on UDP-glucuronosyltransferase using lamotrigine as a phenotypic probe.

Burger DM, Huisman A, Van Ewijk N, Neisingh H, Van Uden P, Rongen GA, Koopmans P, Bertz RJ.

Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. D.Burger@akf.umcn.nl

Atazanavir (ATV) is known to inhibit UGT1A1-mediated glucuronidation. Here we report the effect of ATV and ATV/ritonavir (RTV) on another UGT1A isoenzyme, UGT1A4. Twenty-one healthy volunteers received a single dose of 100 mg of oral lamotrigine on days 1, 13, and 27; on each occasion blood was sampled before the dose was administered and through 120 h after ingestion of the drug. On days 8-17 the subjects received oral ATV 400 mg q.d. On days 18-30 the subjects received oral ATV 300 mg plus oral RTV 100 mg q.d. Seventeen subjects were evaluable for pharmacokinetic analysis. Geometric mean ratios (+90% confidence intervals (CIs)) of lamotrigine area under the plasma concentration-time curve (AUC)(0-inf) and peak plasma concentration (C(max)) for ATV + lamotrigine and for lamotrigine alone were 0.88 (0.86-0.91) and 0.99 (0.95-1.02), respectively; the corresponding ratios for ATV/RTV and for lamotrigine were 0.68 (0.65-0.70) and 0.94 (0.90-0.97), respectively. The mean ratio of lamotrigine-2N-glucuronide to lamotrigine AUC(0-inf) increased from 0.45 for lamotrigine to 0.71 for ATV/RTV + lamotrigine. ATV alone does not significantly influence glucuronidation of lamotrigine. In contrast, ATV/RTV results in moderately decreased exposure to lamotrigine.

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PMID: 18528434 [PubMed - in process]