Drugs online research references








Clin Pharmacokinet. 1985 Jan-Feb;10(1):80-90.
Carbamazepine metabolism in man. Induction and pharmacogenetic aspects.

Eichelbaum M, Tomson T, Tybring G, Bertilsson L.

The metabolism of carbamazepine (CBZ) was studied in 3 groups of subjects: (1) 6 healthy volunteers given a single dose of 200mg carbamazepine; (2) 4 epileptic patients on carbamazepine monotherapy; and (3) 5 patients receiving carbamazepine in combination with other anticonvulsants. Carbamazepine kinetics in the patients were investigated by use of 15N-CBZ. The mean plasma clearances of carbamazepine were 19.8, 54.6 and 113.3 ml/h/kg in groups 1, 2 and 3, respectively. The increased clearance in the patients was mainly due to an induction of the epoxide-diol pathway, as reflected by an increased urinary excretion of the trans-CBZ-diol metabolite. The urinary excretion (as a percentage of the administered dose) of 9-hydroxymethyl-10-carbamoyl-acridan (9-OH-CBZ) was also increased, whereas the excretion of 2-OH-CBZ and 3-OH-CBZ in groups 2 and 3 were decreased in comparison with group 1. As it has been suggested that 9-OH-CBZ is formed from carbamazepine-10,11-epoxide (CBZ-E) or trans-CBZ-diol, the formation of 9-OH-CBZ was investigated in 3 patients with trigeminal neuralgia treated with carbamazepine or CBZ-E as monotherapy on separate occasions. The urinary excretion of 9-OH-CBZ was 1.9, 3.3 and 4.0% of the trans-CBZ-diol excretion during CBZ-E therapy and 23, 32 and 24%, respectively, during carbamazepine administration. Thus only a minor part of the 9-OH-CBZ excreted in urine during carbamazepine therapy is formed via the epoxide-diol pathway. Data on plasma concentrations of carbamazepine and CBZ-E, and on urinary excretion of trans-CBZ-diol from 4 patients on carbamazepine therapy were used to calculate the plasma clearance of CBZ-E. The hydration of CBZ-E during carbamazepine therapy was found to be induced, but to a lesser extent than the epoxidation of carbamazepine. The interrelationship between carbamazepine-epoxidation and oxidative metabolic reactions of some other drugs was also studied in 8 healthy volunteers. Carbamazepine-epoxidation was not correlated to 4-hydroxylation of debrisoquine, oxidation of sparteine, 3- and 4-hydroxylation and demethylation of antipyrine, demethylation of amitriptyline, or total metabolism of theophylline.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3971637&dopt=Abstract

Jpn J Pharmacol. 1966 Sep;16(3):250-6.
Further evidence of central muscle relaxant activity of imipramine, desmethylimipramine and amitriptyline.

Sinha JN, Jaju BP, Srimal RC.

PMID: 5298305


J Chromatogr. 1984 Jun 8;308:165-79.
Amitriptyline and its basic metabolites determined in plasma by gas chromatography.

Burch JE, Roberts SG, Raddats MA.

Gas chromatography was used to determine plasma levels of amitriptyline, nortriptyline and their 10-hydroxy derivatives after conversion to the dehydro compounds by heating with acid. The primary amine 10-hydroxydesmethylnortriptyline is also dehydrated and the dehydro compound coincides on the chromatogram with dehydronortriptyline. Treatment of the extract with salicylaldehyde selectively removed the primary amine, which was determined by difference. Cis- and trans-hydroxydesmethylnortriptyline were isolated from urine by thin-layer chromatography and used to standardize the estimation. The stability of all the metabolites in plasma was investigated. Results are given for hydroxydesmethylnortriptyline levels in the plasma of 41 patients treated with amitriptyline.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6746812&dopt=Abstract












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