Population Pharmacokinetics Modeling of Lamotrigine in Jordanian Epileptic Patients Using Dried Blood Spot Sampling
| Autor: | Amira Masri, Abdelkarim A. Al-Qudah, Maysa Suyagh, Yasmeen I. Dodin, Abdallah M. Younes, Ziad T. Nuseir, Salah AbuRuz, Mohammad Saleh, Mutasim Al-Ghazawi |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Phenytoin Topiramate medicine.medical_specialty Lamotrigine Models Biological 030226 pharmacology & pharmacy Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine Drug Discovery medicine Humans Child Valproic Acid Epilepsy business.industry General Medicine Carbamazepine NONMEM Dried blood spot Anticonvulsants Phenobarbital business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Drug Research. 71:429-437 |
| ISSN: | 2194-9387 2194-9379 |
| DOI: | 10.1055/a-1524-0913 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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