The effect of raltegravir on the glucuronidation of lamotrigine.
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 (AUC(0-->48)) and peak plasma concentration (C(max)) 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 AUC(0-->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.
van Luin
Matthijs
M
Department of Clinical Pharmacy, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands. m.vanluin@akf.umcn.nl
Colbers
Angela
A
Verwey-van Wissen
Corrien P W G M
CP
van Ewijk-Beneken-Kolmer
Eleonora W J
EW
van der Kolk
Mike
M
Hoitsma
Arjen
A
da Silva
Hugo Gomes
HG
Burger
David M
DM
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D014227:Triazines; D000068898:Raltegravir Potassium; D014453:Glucuronosyltransferase; D000077213:Lamotrigine