title: Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis.
abstract: The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.
authors.affiliation: *Department of Pharmacy, Faculty of Medicine; ‡Division of Neurology, Faculty of Medicine; and †Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Yeap
authors.forename: Kheng-Seang
authors.initials: KS
authors.lastname: Lim
authors.forename: Ching-Ching
authors.initials: CC
authors.lastname: Ng
authors.forename: Amy
authors.initials: A
authors.lastname: Hui-Ping Khor
authors.forename: Yoke-Lin
authors.initials: YL
authors.lastname: Lo
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013956:Antithyroid Agents / Q000627:therapeutic use; D002220:Carbamazepine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002231:Carbimazole / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy / Q000503:physiopathology; D008296:Malaysia; D055118:Medication Adherence; D000089762:Multidrug Resistance-Associated Protein 2; D011110:Polymorphism, Genetic; D011433:Propranolol / Q000627:therapeutic use; D013971:Thyrotoxicosis / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: C000715087:ABCC2 protein, human; D000927:Anticonvulsants; D013956:Antithyroid Agents; D000089762:Multidrug Resistance-Associated Protein 2; D002220:Carbamazepine; D002231:Carbimazole; D011433:Propranolol