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Population Pharmacokinetics of Lamotrigine in Elderly Patients

From Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (Ms Punyawudho, Dr Brundage, Dr Birnbaum); VA Medical Center, Miami, Florida (Dr Ramsay, Ms Macias); VA Medical Center, Bronx, New York (Dr Rowan); and VA Medical Center, Perry Point, Maryland (Dr Collins).

Lamotrigine is being used more frequently in elderly patients. Dosing of lamotrigine in elderly patients is based largely on studies from younger adults and not evidence-based data from elderly patients. The goal of this study is to determine the pharmacokinetic parameters, such as clearance, and the factors that have a significant effect on these parameters to provide evidence-based information that can be used to dose elderly patients taking lamotrigine. Lamotrigine plasma concentrations from 148 elderly patients (aged 59-92 years) were used to develop a population pharmacokinetic model. Data were analyzed using NONMEM. Model evaluation was performed using the bootstrap approach and predictive check. The results showed that the blood urea nitrogen/serum creatinine ratio, weight, and phenytoin use significantly affect apparent clearance of lamotrigine. These results show that clinicians may need to take into account these covariates when dosing lamotrigine in this population.

Key Words: NONMEM • lamotrigine • elderly • population pharmacokinetics

Address for correspondence: Angela K. Birnbaum, PhD, University of Minnesota, Experimental and Clinical Pharmacology, 7-170 WDH, 308 Harvard St SE, Minneapolis, MN 55455; e-mail: birnb002{at}umn.edu.

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