Pharmacokinetic Data of Carbamazepine and Its Major Metabolites in Man

Faigle, J. W.; Feldmann, K. F.

doi:10.1007/978-3-642-85921-2_15

Cited by 43 publications

(31 citation statements)

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“…Only minor quantities of unchanged carbamazepine (about 2 % of the dose) is found in human urine (Faigle and Feldmann, 1975;Morselli et aI., 1975). Most of the drug is metabolised and 2 oxidative pathways have been recognised in man.…”

Section: Metabolismmentioning

confidence: 97%

“…After the administration of a single oral dose of '4C-carbamazepine to 2 volunteers, 72 % of the administered radioactivity was excreted in the urine and the rest in faeces over a period of 9 days (Faigle and Feldmann, 1975). The slow appearance of radioactivity in faeces suggests that it had been absorbed in the gastrointestinal tract and then excreted via the bile.…”

Section: Metabolismmentioning

confidence: 97%

“…However, based on the recovery of radio-labelled carbamazepine in urine and faeces, the oral bioavailability of the drug (in gelatin capsule) is more than 70 % (Faigle and Feldmann, 1975). The areas under the plasma concentration-time curve (AUC) extrapolat~ to infinite time are similar when the drug is given as a tablet or as a solution in aqueous ethanol (Rawlins et aI., 1975) or in propylene glycol (Levy et aI., 1975b).…”

Section: Fundamental Properties In Volunteers and Patientsmentioning

confidence: 98%

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Clinical Pharmacokinetics of Carbamazepine

Bertilsson

1978

Clinical Pharmacokinetics

211

108

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Carbamazepine seems to as effect as phenytoin in the treatment of grand mal and psychomotor epilepsy. It is the drug of first choice in trigeminal neuralgia. After single oral doses of carbamazepine, the absorption is fairly complete and the elimination half-life is about 35 hours (range 18 to 65 hours). During multiple dosing, the half-life is decreased to 10-20 hours, probably due to autoinduction of the oxidative metabolism of the drug. Phenytoin and barbiturates also induce the metabolism of carbamazepine. After single doses of carbamazepine, elimination follows dose-dependent first order kinetics. Carbamazepine is metabolised by oxidation before excretion in the urine. In experimental animals, the metabolite carbamazepine-10,11-epoxide has anticonvulsant activity comparable with that of the parent drug. The plasma concentration of the metabolite during long-term treatment of epileptic patients varies between 5 and 81% of that of the parent drug. The plasma protein binding of the metabolite is about 50% compared with about 75% for the parent drug. Less than 50% of a given carbamazepine doses has been identified as metabolites in the urine. The quantitatively most important metabolites is the trans-10,11-dihydro-10,11-diol. The kinetics of carbamazepine have been explored to some extent in pregnant women, newborns and children. Plasma levels of carbamazepine seem to decrease during pregnancy, possibly as a result of increased metabolism. The drug readily crosses the placenta and the levels measured in newborns are comparable with maternal plasma concentrations. In newborns exposed to the drug during fetal life, the plasma half-lives were relatively short (8.2 to 28.1 hours) indicating an induction of carbamazepine metabolism during gestation. The pharmacokinetics of carbamazepine in children aged 0.3 to 15 years are comparable with that in adults. A single daily dose of carbamazepine is insufficient; 2 doses per day are appropriate in most cases, but some patients may benefit from more frequent dosing to avoid side-effects. Compared with phenytoin, for example, very few controlled studies have been performed to establish the plasma level range of carbamazepine associated with the best therapeutic outcome. However, the best anticonvulsant effect of carbamazepine seems to be obtained at plasma levels of about 5 to 10microgram/ml (20 to 40mumol/L). Side-effects are most frequent at higher levels but may also be seen at lower levels.

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Section: Metabolismmentioning

confidence: 97%

Section: Metabolismmentioning

confidence: 97%

Section: Fundamental Properties In Volunteers and Patientsmentioning

confidence: 98%

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Clinical Pharmacokinetics of Carbamazepine

Bertilsson

1978

Clinical Pharmacokinetics

211

108

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“…In rats, the largest portion of CBZ is biotransformed to CBZ-epoxide by the microsomal epoxidation pathway [14]; however, in humans, about 90% of CBZepoxide is further metabolized to 10,11-transdiol by epoxide hydrolase [14]. Tateishi et al [19] suggested that there are more enzymes, such as CYP 2C6 and CYP 2C11, that are involved in CBZ metabolism in rats than in human.…”

Section: Pharmacokinetics Of Carbamazepinementioning

confidence: 99%

“…The four major metabolic pathways of CBZ in humans are the epoxide pathway, aromatic hydroxylation, direct N-glucuronidation, and sulfur-containing conjugation, and metabolites from these pathways constitute 40%, 25%, 15%, and 5% of urinary excreted drug, respectively. The epoxide pathway is mediated by cytochrome P450, such as CPY3A4 and CPY2B, which can be induced by the repeated administration of CBZ to both humans and animals [14][15][16][17][18][19], leading to increased metabolic clearance. CBZ metabolism and pharmacokinetics can be altered by many drugs, such as phenytoin and phenobarbital which increase CBZ clearance and other drugs as cimetidine, erythromycin, and isoniazid, which inhibit the activity of the cytochrome P450 system, decreasing the clearance of CBZ [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

Lin

Lee²,

Ravis³

2013

Clin Exp Pharmacol

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Objectives: To investigate the pharmacokinetics of Carbamazepine (CBZ) in rats during growth hormone treatment.Methods: Recombinant Human Growth Hormone (rhGH) was injected subcutaneously at a daily dose of 0.1 mg/ kg, 2 mg/kg, or phosphate buffered saline (control) for 5 days in male Sprague-Dawley rats. On day 6, a dose of 25 mg/kg of CBZ was injected intravenously via a jugular vein cannula into the rat. Growth rate were compared between treatment groups. The pharmacokinetics of CBZ was determined from its concentrations in rats' blood and urinary samples.Results: Over the 5-day treatment period, growth rate were greater than control for the 2 mg/kg rhGH dosed group. The volume of distribution (V ss ) was significantly (p<0.05) decreased in the high dosed rhGH rats compared to the control group. Total body clearance (CL) in the 2 mg/kg rhGH group was also significantly (p<0.05) decreased compared with the control group (0.497 ± 0.076 L/hr/kg vs 0.685 ± 0.109 L/hr/kg). Urinary data showed that renal and metabolic clearances were both significantly (p<0.05) decreased in the 2 mg/kg rhGH group. Conclusions:A dose dependent effect of rhGH was observed on growth rates and CBZ pharmacokinetics in rats. After 5 days rhGH treatment, the volume of distribution of CBZ was significantly changed in the 2 mg/kg/day rhGH treated groups. In the 2 mg rhGH/kg treated rats, both renal and metabolic clearance of CBZ were also significantly decreased compared with the control group. Similar decreases in volume of distribution and both clearances may suggest the interaction may involve increased CBZ plasma protein binding during rhGH treatment in rats.

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