Reference

The metabolism of carbamazepine in humans: steric course of the enzymic hydrolysis of the 10,11-epoxide

The metabolism of carbamazepine in humans: steric course of the enzymic hydrolysis of the 10,11-epoxide. Bellucci, Giuseppe; Berti, Giancarlo; Chiappe, Cinzia; Lippi, Annalisa; Marioni, Franco (Fac. Farm., Univ. Pisa, Pisa, Italy). J. Med. Chem., 30(5), 768-73 (English) 1987. CODEN: JMCMAR. 9048-63-9 and 39637-99-5 which are cas registry numbers are also used here. ISSN: 0022-2623. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 7, 27 Carbamazepine 10,11-oxide (I) [36507-30-9], a key intermediate in carbamazepine [298-46-4] metab., is unusually resistant to enzymic hydrolysis when incubated with microsomal and cytosolic fractions from rabbit, rat, or guinea pig livers. However, its hydrolysis product, trans-10,11-dihydroxy-5H-dibenzo[b,f]azepine-5-carboxyamide, is excreted, as previously reported, both in the free and in conjugated forms, as the main metabolite in the urine of humans under carbamazepine treatment. The free diols, and those obtained after treatment with b-glucuronidase-arylsulfatase, were formed in an enantiomeric excess of 80%, the prevalent enantiomer having the (-)-10S,11S abs. configuration. As this finding confirms the pronounced enantioselectivity of the microsomal epoxide hydrolase [9048-63-9] toward meso and racemic substrates, but is in contrast with the prevalent formation of (R,R)-diols in most other known cases of enzymic hydrolysis of epoxides. The prepn. of racemic carbamazepine trans-10,11-dihydro-10,11-diol [106680-78-8] and 9-(hydroxymethyl)-10-carbamoylacridan, [68011-71-2] another carbamazepine metabolite, is reported for the 1st time. .

Use of unbound drug concentrations to determine neonatal anticonvulsant exposure

Use of unbound drug concentrations to determine neonatal anticonvulsant exposure. Friel, Patrick N.; Yerby, Mark S.; McCormick, Karen B. (Sch. Med., Univ. Washington, Seattle, WA 98104, USA). Epilepsy Res., 1(1), 70-3 (English) 1987. CODEN: EPIRE8. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Unbound and total concns. of several anticonvulsant drugs were measured by liq. 125-33-7 and 58955-93-4 which are cas registry numbers are also used here. chromatog. in maternal and neonatal cord serum collected at birth from 16 women being treated for epilepsy and their newborns. Maternal and neonatal unbound drug concns. agreed closely for phenobarbital [50-06-6] (n = 6), phenytoin [57-41-0] (n = 7), carbamazepine [298-46-4] (n = 8), and its epoxide metabolite [36507-30-9]. Mean maternal total drug concns. were higher than neonatal concns. in the cases of phenobarbital, carbamazepine, its epoxide and diol metabolite [58955-93-4]. The differences were due to greater protein binding in maternal serum. Measurement of total anticonvulsant concns. in newborns may be misleading, because of altered protein binding in the neonate. For the medications tested, neonatal and maternal exposures to unbound drug appear to be equiv. .