The Effect of Raltegravir on the Glucuronidation of Lamotrigine

• Published in: Journal of clinical pharmacology Vol. 49; no. 10; pp. 1220 - 1227
• Main Authors: van Luin, Matthijs, Colbers, Angela, Verwey-van Wissen, Corrien P. W. G. M., van Ewijk-Beneken-Kolmer, Eleonora W. J., van der Kolk, Mike, Hoitsma, Arjen, da Silva, Hugo Gomes, Burger, David M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2009; SAGE Publications
• Subjects: Adult; Anticonvulsants - administration & dosage; Anticonvulsants - pharmacokinetics; Drug Administration Schedule; Drug Interactions; Drug-drug interactions; glucuronidation; Glucuronosyltransferase - antagonists & inhibitors; HIV Integrase Inhibitors - administration & dosage; HIV Integrase Inhibitors - adverse effects; HIV Integrase Inhibitors - pharmacokinetics; Humans; lamotrigine; Male; Medication Adherence; Middle Aged; Pyrrolidinones - administration & dosage; Pyrrolidinones - adverse effects; Pyrrolidinones - pharmacokinetics; raltegravir; Raltegravir Potassium; Triazines - administration & dosage; Triazines - pharmacokinetics
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270009345689

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.