Pharmacokinetic study of carbamazepine and its carbamazepine 10,11-epoxide metabolite in a group of female epileptic patients under chronic treatment.
BACKGROUND
Although epileptic crises are equally frequent in women and men, several factors cause female epileptics to present a series of gender-specific problems. To date, few studies have been published on the kinetics of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-E) active metabolite in a Mexican population, and no information for epileptic women of reproductive age is available. The aim of the present work was to study the pharmacokinetic behavior of this group of women during steady state.


METHODS
Fourteen epileptic women under chronic treatment receiving only the anticonvulsant CBZ to control their crises were studied. A blood sample was taken before breakfast, before the morning dose of 200 mg, and after the dose at 1, 2, 3, 4, 5, and 8 h. Serum was separated by centrifugation at 1,350 x g. Serum concentrations of carbamazepine (CBZ) and of the metabolite carbamazepine 10,11-epoxide (CBZ-E) were measured by HPLC. Pharmacokinetic parameters were calculated by statistical moment method after obtaining serum concentrations.


RESULTS
Maximum time (T(max)) for CBZ was reached at 2.72+/-0.71 h and for CBZ-E, it was 3.60+/-0.79 h. C(max) for CBZ was 7.30+/-2.30 microg/mL, while C(min) for CBZ was 6.30+/-2.49. Maximum serum values for CBZ-E were 1.01+/-0.57, equivalent to 13.80% of CBZ; t(12) value for CBZ and CBZ-E was 18.20 and 16.10 h, respectively. AUC values for CBZ and metabolite were 70.33+/-17.10 microg/L/h and 9.20+/-2.50 microg/L/h, respectively. CBZ and CBZ-E clearance did not show differences and were 0.37 mL/kg/min and 0.40 mL/kg/min, respectively. Extraction index for serum concentrations of CBZ and CBZ-E AUC(CBZ)/AUC(CBZ-E) was 0.13; positive correlation was observed between serum concentrations of CBZ and E-CBZ, with r=0.94.


CONCLUSIONS
The schedule we suggest for therapeutic monitoring of serum concentrations of CBZ in chronic treatments is 3 h for maximum peak concentration of C(max) after dose administration and for minimum peak concentration, C(min) prior to subsequent administration of the dose.
Moreno
Julia
J
Laboratorio Clínico, Dirección de Servicios Clínicos, Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente, Calzada Mexico-Xochimilco 101, San Lorenzo Huipulco, Tlalpan, 14370 México City, D.F., México. moreno@imp.edu.mx
Belmont
Aurora
A
Jaimes
Orlando
O
Santos
José A
JA
López
Guadalupe
G
Campos
María G
MG
Amancio
Octavio
O
Pérez
Patricia
P
Heinze
Gerardo
G
D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007700:Kinetics; D008800:Mexico; D013997:Time Factors
D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide