J Clin Pharmacol
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0091270009345689v1
49/10/1220    most recent
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DRUG INTERACTIONS

The Effect of Raltegravir on the Glucuronidation of Lamotrigine

Matthijs van Luin, PharmD, Angela Colbers, MSc, Corrien P. W. G. M. Verwey-van Wissen, Eleonora W. J. van Ewijk-Beneken-Kolmer, Mike van der Kolk, PhD, Arjen Hoitsma, MD, Hugo Gomes da Silva, MD and David M. Burger, PharmD, PhD

From Radboud University Nijmegen Medical Centre, Department of Clinical Pharmacy, Nijmegen, The Netherlands (Dr van Luin, Ms Colbers, Dr Verwey-van Wissen, Dr van Ewijk-Beneken-Kolmer, Dr Burger); Nijmegen Institute for Infection, Inflammation and Immunology (N4i), Nijmegen, The Netherlands (Dr van Luin, Ms Colbers, Dr Burger); Rijnstate Hospital, Department of Clinical Pharmacy, Arnhem, The Netherlands (Dr van Luin); Clinical Research Centre, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (Dr van der Kolk, Dr Hoitsma); and Merck Research Laboratories, EMEAC, Munich, Germany (Dr da Silva).

The authors studied the effect of raltegravir on the pharmacokinetics of the antiepileptic agent lamotrigine. Twelve healthy volunteers (group A) received 400 mg raltegravir twice daily from days 1 to 5. On day 4, a single dose of 100 mg lamotrigine was administered. After a washout period, participants received a second single dose of 100 mg of lamotrigine but now without raltegravir (day 32). In group B, 12 participants received the same treatment as in group A but in reverse order. On days 4 and 32, 48-hour pharmacokinetic curves were drawn. Geometric mean ratios (+90% confidence intervals [CIs]) of lamotrigine area under the plasma concentration-time curve (AUC0->48) and peak plasma concentration (Cmax) for raltegravir + lamotrigine versus lamotrigine alone were 0.99 (0.96-1.01) and 0.94 (0.89-0.99), respectively. The mean ratio of the AUC0->48 of lamotrigine-2N-glucuronide to lamotrigine was similar when lamotrigine was taken alone (0.35) or when taken with raltegravir (0.36). Raltegravir does not influence the glucuronidation of lamotrigine.

Key Words: Drug-drug interactions • raltegravir • glucuronidation • lamotrigine

Address for reprints: Matthijs van Luin, Department of Clinical Pharmacy, 864, Radboud University Medical Centre Nijmegen, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands; e-mail: m.vanluin{at}akf.umcn.nl.


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