Single and multiple dose kinetics of a new antiepileptic drug, Org 6370, and its desmethyl metabolite, Org 6363.
The pharmacokinetic parameters of the new antiepileptic drug, Org 6370, and its desmethyl metabolite, Org 6363, were studied in healthy male volunteers. Plasma concentrations of the compounds were determined by a new method using liquid-solid extraction and capillary gas-chromatographic separation with a nitrogen-selective detector. The kinetic parameters obtained after a single oral dose of Org 6370 were not good predictors of multiple-dose parameters. With long-term treatment, there was unanticipated accumulation of the parent drug and especially the metabolite. The clinical implication of these findings is that caution must be exercised in clinical trials of Org 6370.
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism* / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002849:Chromatography, Gas; D004827:Epilepsy / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D013997:Time Factors
D000927:Anticonvulsants; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; C049281:5,6,9,10-tetrahydro-N,N-dimethyl-5,9-methanobenzocycloocten-11-amine; C049284:5,6,9,10-tetrahydro-N-methyl-5,9-methanobenzocycloocten-11-amine