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Drug Res (Stuttg) 2021; 71(08): 429-437
DOI: 10.1055/a-1524-0913
Original Article

Population Pharmacokinetics Modeling of Lamotrigine in Jordanian Epileptic Patients Using Dried Blood Spot Sampling

Yasmeen I. Dodin   *
1   Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
,
Maysa F. Suyagh
1   Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
,
Mohammad I. Saleh   *
1   Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
,
Ziad T. Nuseir   **
2   Division of Neurology, Department of Internal Medicine, Faculty of Medicine, The University of Jordan, Amman, Jordan
,
Salah M. Aburuz
1   Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
,
Abdelkarim A. Al-Qudah
3   Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, The University of Jordan, Amman, Jordan
,
Amira T. Masri
3   Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, The University of Jordan, Amman, Jordan
,
Abdallah M. Younes
4   Private Neurology Clinic, Amman, Jordan
,
Mutasim A. Al-Ghazawi
1   Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan
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Abstract

Aims To characterize the population pharmacokinetics of lamotrigine in Jordanian epileptic patients and to identify factors affecting therapeutic parameters.

Patients and Methods A population pharmacokinetics model for lamotrigine was established based on a prospectively collected data of 52 steady-state concentrations from 38 adult and pediatric patients with epilepsy. Lamotrigine concentrations were determined by a dried blood spot liquid chromatography method. Data were analyzed according to a one-compartment model with first-order absorption and elimination using the nonlinear mixed effect modeling program. The covariates effect of total body weight, gender, age, and co-medication with topiramate, carbamazepine, phenytoin, phenobarbital, and valproic acid on lamotrigine clearance were investigated using a stepwise forward addition followed by a stepwise backward elimination.

Results The final population pharmacokinetics model for lamotrigine clearance was as follows: CL/Fpop=θ1*exp (θ3*age)*exp (θ5*carbamazepine)*exp (θ6*valproic acid) , where θ1 is the relative clearance (L/hr) estimated, and θ3, θ5, and θ6 are the fixed parameters relating to age and co-medication with carbamazepine and valproic acid, respectively.The population mean value of lamotrigine total clearance generated in the final model (with covariates) was 2.12 L/hr. Inter-individual variability and residual unexplained variability expressed as the coefficient of variation was 37.1 and 26.1%, respectively.

Conclusion Lamotrigine total clearance in the Jordanian patients is comparable to that reported by others for Caucasian patients. Age and concomitant therapy with carbamazepine and valproic acid significantly affected lamotrigine clearance, and accounted for 48% of its inter-individual variability.

Key words

Lamotrigine - Population pharmacokinetics - NONMEM - Jordanian population - Dried blood spot.

* at the time of study. Current affiliation: Cancer Control Office, King Hussein Cancer Center, Amman, Jordan


** at the time of study. Current affiliation: Private Neurology Clinic, Amman, Jordan


*** at the time of the study. Current affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates




Publication History

Article published online:
12 July 2021

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