LC/MS/MS를 이용한 가바펜틴 300 mg 캡슐의 성인 지원자에 대한 생물학적 동등성 및 약물동태 연구

Abstract

Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is a new antiepileptic drug related to γ-aminobutyric acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced 2x2 crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatographytandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. WinNonlin®, the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by 1/(predicted y)2 was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters (AUC0-24hr, AUCinf, Cmax and Tmax) and other parameters (Ka, Kel, Vd/F and Cl/F) of Gapentin TM (test drug) and Neurontin TM (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed AUC0-24hr and Cmax were log(0.9106)~log(1.1254) and log(0.8521)~log(1.0505), respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.