니세틸 정(아세틸-엘-카르니틴 500 mg)에 대한 뉴로세틸 정의 생물학적 동등성

Bioequivalence of Neurocetil Tablet to Nicetile Tablet (Acetyl-L-Carnitine 500 mg)

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, $Nicetile^{TM}$ (Dong-A pharmaceutical Co., Ltd.) and $Neurocetil^{TM}$ (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, $22.80{\pm}2.76$ year in age and $63.07{\pm}7.98\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the $Nicetile^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 94.87% and 87.17%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 15.58% and 19.16% $AUC_t\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-11.84{\sim}6.41$ and $-10.57{\sim}11.88$for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Neurocetil^{TM}$ tablet is bioequivalent to $Nicetile^{TM}$ tablet.