Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy.

Abstract

Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18-61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naive controls, monotherapy and co-VPA decreased CBZ t1/2 by 50%, and more than doubled the CBZ Cl without a significant change in the Vd. Autoinduction is one explanation for these changes with chronic CBZ therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: R E Ramsay, D Q McManus, A Guterman, T V Briggle, D Vazquez, R Perchalski, R A Yost, P Wong
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 12 Issue 3 Pg. 235-41 (May 1990) ISSN: 0163-4356 [Print] United States
• PMID: 2112276 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carbamazepine
• Valproic Acid
• Phenytoin
• carbamazepine epoxide
• Phenobarbital

Topics

• Administration, Oral
• Adolescent
• Adult
• Carbamazepine (administration & dosage, analogs & derivatives, blood, metabolism)
• Chromatography, High Pressure Liquid
• Drug Interactions
• Drug Therapy, Combination
• Epilepsy (blood, drug therapy)
• Female
• Half-Life
• Humans
• Male
• Middle Aged
• Phenobarbital (administration & dosage, therapeutic use)
• Phenytoin (administration & dosage, therapeutic use)
• Protein Binding (drug effects)
• Valproic Acid (administration & dosage, therapeutic use)