M. Jovanovic (1), D. Sokic (2) I. Grabnar (3), T.Vovk (3), M. Prostran (4), K. Vucicevic (1), B. Miljkovic (1)
(1) Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Serbia; (2) Clinic of Neurology, Clinical Centre of Serbia, Belgrade; (3) Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Ljubljana, Slovenia; (4) Departmant of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Serbia.
Objectives: The aim of the study was to investigate influence of carbamazepine (CBZ) on topiramate (TPM) oral clearance (CL/F) in adult patients with epilepsy.
Methods: Data were collected from 78 adult epilepsy patients on mono- or co-therapy of TPM and other antiepileptic drug(s). Daily doses of TPM were in range from 50 – 1200 mg and dosage regimens were once, twice or three times a day. One to two blood samples were taken per patients in steady-state. Patients co-treated with CBZ administered doses in range from 300 – 1600 mg. The population pharmacokinetic (PK) analysis was performed using NONMEM® software (version 7.2).
Results: A one-compartment model with first-order absorption and elimination was used as a structural model. The interindividual variability was evaluated by an exponential model while residual variability was best described by proportional model. Volume of distribution was estimated at 0.575 (0.499 – 0.651) l/kg. TPM CL/F was significantly (p < 0.001) influenced by CBZ daily dose. The estimate of CL/F for a typical patient was 1.534 (1.448 – 1.612) l/h while the interindividual variability in studied population was 16.514% (11.780 – 20.166%). Mean TPM CL/F during CBZ co-therapy was higher for 60.78% than in patients not co-treated with CBZ. The stability of the model was confirmed by bootstrap resampling technique.
Conclusions: Final population PK model quantifies influence of CBZ daily dose on TPM CL/F. The results from the study allow individualization of TPM dosing in routine patient care, especially useful for patients on different CBZ dosing regimens.
Reference: PAGE 22 () Abstr 2764 [www.page-meeting.org/?abstract=2764]
Poster: CNS