Early stage autoinduction of carbamazepine metabolism in humans

✍ Scribed by I. Bernus; R. G. Dickinson; W. D. Hooper; M. J. Eadie

• Publisher: Springer
• Year: 1994
• Tongue: English
• Weight: 581 KB
• Volume: 47
• Category: Article
• ISSN: 0031-6970
• DOI: 10.1007/bf00191168

✦ Synopsis

Six healthy young adult male volunteers were given two 600 mg (2540 g moles) oral doses of carbamazepine (CBZ) 5 days apart. Serial concentrations of CBZ and its 10,11-epoxy (CBZ-epoxide) and 10,11-dihydro-lO,11-trans-dihydroxy (CBZ-diol) metabolites in plasma, and daily excretions of these substances and the 2-hydroxy (2-OH-CBZ), 3-hydroxy (3-OH-CBZ) and 9-hydroxymethyl-10-carbamoylacridan (acridan) metabolites in urine were followed for 5 days after each dose.

Pharmacokinetic analysis showed that autoinduction of CBZ metabolism was present within 6-10 days of the initial drug dose. The mean oral clearance of CBZ increased from 1.48 to 1.74 1 -h 1 (difference 0.26 1. h -1, 95 % confidence interval 0.11 to 0.411-h 1) and the mean percentage urinary recovery of the amount of CBZ eliminated increased from 41.8 % to 44.6 % (difference 2.8 %, 95 % confidence interval 0.5 to 5 %) between the two studies 5 days apart.

The data for daily clearance to metabolite and the time-courses of the plasma CBZ-epoxide to CBZ and CBZ-diol to CBZ concentration ratios suggested that autoinduction had begun by the second day after CBZ intake, and involved not only the epoxide-diol pathway but, to a lesser extent, the oxidations to phenolic derivatives.