A single-dose study to define tiagabine pharmacokinetics in pediatric patients with complex partial seizures
| Autor: | G. R. Granneman, Kenneth W. Sommerville, S. W. Boellner, L. E. Gustavson, T. El-Shourbagy, J. X. Qian, H. J. Guenther |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Phenytoin Tiagabine medicine.medical_treatment Nipecotic Acids Epilepsy Complex Partial Elimination rate constant Pharmacokinetics medicine Humans Child Body surface area business.industry Valproic Acid Carbamazepine Anticonvulsant Child Preschool Anesthesia Concomitant Body Constitution Anticonvulsants Drug Therapy Combination Female Sleep Stages Neurology (clinical) business medicine.drug |
| Zdroj: | Neurology. 48:1032-1036 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.48.4.1032 |
| Popis: | We report an open-label study of 25 children with complex partial seizures that assessed the pharmacokinetics and safety of a single dose of approximately 0.1 mg/kg tiagabine. The children received their usual individualized regimen of one concomitant antiepilepsy drug (AED) throughout the study. Seventeen children were receiving an inducing AED (carbamazepine or phenytoin); eight were receiving valproate. Tiagabine was well tolerated. Dose-normalized Cmax was higher in children taking valproate (18.2 +/- 5.0 ng/mL/mg) than in the induced children (14.8 +/- 6.9 ng/mL/mg), but the difference was not statistically significant. Dose-normalized area under the plasma concentration-time curve from time zero to infinite time was significantly higher (p = 0.002) in children taking valproate (176.5 +/- 54.7 ng.hr/mL/mg) than in induced children (92.4 +/- 56.7 ng.hr/mL/mg). Similarly, oral clearance in the children taking valproate (96 +/- 39 mL/min) was half that of the induced children (207 +/- 91 mL/min). Half-life in children taking valproate (5.7 hr) was almost twice that for the induced children (3.2 hr), and the elimination rate constant was significantly lower (p0.02) for the children taking valproate than for the induced children. Volume of distribution was similar in the children taking valproate (52 +/- 9 L) and the induced children (59 +/- 29 L). This is consistent with observations in adults taking tiagabine with inducing AEDs or valproate. Exploratory regressions on these data in children and previous data in adults showed fairly strong relationships between body size and tiagabine clearance and volume of distribution, with body size explaining about 40 to 50% of the variability. When adjusted per kg body weight, clearance and volume were greater in children than adults. When adjusted per m2 body surface area, clearance and volume were more similar in adults and children. |
| Databáze: | OpenAIRE |
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