Relative Bioavailability of Controlled Release Carbamazepine and Pharmacokinetic Properites : Steady-State Study

J Korean Neurol Assoc > Volume 10(3); 1992 > Article

Journal of the Korean Neurological Association 1992;10(3): 316-323.

Carbamazepine 서방형 제제의 상대적 생체이용율 및 약동학적 성상 : 항정상태에서의 연구

김재일, 신상구,명호진

경상대학교 신경과. 서울대학교 약리학, 신경과.

Relative Bioavailability of Controlled Release Carbamazepine and Pharmacokinetic Properites : Steady-State Study

Jae-Ill Kim, M.D., Sang-Ku Shin, M.D., Ho-Jin Myung, M.D.

Department of Neurology, College of Medicine, Gyeongsang National University, Department of Neurology and Pharmacology, College of Medicine, Seoul National University

Abstract

The relative bioavailability amd palsma level fluctuation of controlled release carbamazepine (carbamazepine CR, CBZ CR, Tegretol CR) to the regular product (Carbamazepine RR, CBZ RR, Tegletol RR) were studied in 12 patients who were taking stable dose of carbamazepine for more than six weeks. Fixed dosage regimen (400 mg every 12 hours) of both products was administered in a random cross over manner at least for four days. After reaching steady-state, serial blood samples were drawn after last dose administration. Plasma carbamazepine levels were analysed by fluorescence polarizing immunoassay. The controlled lelease products showed lower area under the concentration time curve (AUC; 89.7)20.0 ug/ml/hr) than that (107.1)13.2 ug/ml/hr) of the regular products (p<0.01), and also showed low peak plasma level (CR;848)l.93ug/ml, RR;10.57+1.55 ug/ml). However. Fluctuation of plasma drug level during dose interval was slightly less in controlled release products compared with carbamazepine regular products in the respect of various indices such as percent fluctuation, fluctuation index and area deviation from mean level. However those parameters did not show no statistical singificance between two products except area diviation (p<0.01). Though the controlled relase product showed slightly less fluctuation during dose interval, this seemed to be the expense of incomplete bioavailability. As a conclusion, the dose correction should be made according to the relative bioavailability of controlled release formulation if switching of the formulation from regular to controlled release form would be needed. However it could not be proved that controlled release fromulation had less fluctiuation during dose interval in this study. More detailed studies should be pursued to show the evidence of significant superiority of currently marketing controlled release formulation to the regular one.