PMID: 3750374Jan 1, 1986Paper

Clinical pharmacokinetics of carbamazepine and its epoxy and hydroxy metabolites in humans after an overdose

Therapeutic Drug Monitoring
T B VreeW J Wijnands

Abstract

In five cases of carbamazepine (CBZ) intoxication, the time curves of the plasma concentration and of the renal excretion rate of carbamazepine and its metabolites carbamazepine 10,11-epoxide (CBZ-epoxide) and trans-10,11-dihydro-10,11-dihydroxy-CBZ (CBZ-diol) were measured. Pseudo-steady-state or plateau-like plasma concentration-time curves were observed when doses of 12 or 18 g of CBZ were ingested. Hemoperfusion lowers the plasma concentration of CBZ and its metabolites by affecting the half-life. The effect of hemoperfusion is reduced by the continuous absorption from the gastrointestinal tract and redistribution from the tissues. The renal clearances of CBZ and of CBZ-epoxide are low (1 and 8 ml/min, respectively); both are flow dependent. The renal clearance of CBZ-diol is approximately 160-350 ml/min and is independent of the urine flow. Although urine stimulation increases the renal clearance of CBZ by 100%, the overall amount excreted increases only 1-2% of the dose. Protein binding of CBZ is approximately 80%, of CBZ-epoxide 50%, and of CBZ-diol 70%.

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