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

Yasmeen I. Dodin; Maysa F. Suyagh; Mohammad I. Saleh; Ziad T. Nuseir; Salah M. Aburuz; Abdelkarim A. Al-Qudah; Amira T. Masri; Abdallah M. Younes; Mutasim A. Al-Ghazawi

doi:10.1055/a-1524-0913

Drug Research, Inhaltsverzeichnis

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^*

¹Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan

,

Maysa F. Suyagh

¹Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan

,

Mohammad I. Saleh^*

¹Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan

,

Ziad T. Nuseir^**

²Division of Neurology, Department of Internal Medicine, Faculty of Medicine, The University of Jordan, Amman, Jordan

,

Salah M. Aburuz

¹Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan

,

Abdelkarim A. Al-Qudah

³Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, The University of Jordan, Amman, Jordan

,

Amira T. Masri

³Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, The University of Jordan, Amman, Jordan

,

Abdallah M. Younes

⁴Private Neurology Clinic, Amman, Jordan

,

Mutasim A. Al-Ghazawi

¹Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan

› Institutsangaben

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/F_pop=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.

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Referenzen

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