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2001 (v.9 no.1)

The Journal of Korean Society for Clinical Pharmacology and Therapeutics

Korean Society for Clinical Pharmacology and Therapeutics
ISSN: 1225-5467

  • Bioequivalence Study of Two Terazosin Formulations : TZCTablet and Hytrin Tablet

    Hyeong-Seok Lim, So-Young Yi, Joo-Youn Cho, Kyun-Seop Bae, Kyoung-Sang Yu, In-Jin Jang, Sang-Goo Shin

    J Korean Soc Clin Pharmacol Ther | v.9, no.1, pp.57-65, Jun, 2001


    Background : Terazosin is an tex:\small\textstyle${\alpha}-adrenergic$ receptor blocker and is used for the treatment of mild to moderate hypertension and benign prostatic hyperplasia. Terazosin can be administered once daily because of its high oral bioavailability of about 90% and long half-life of 9 to 12 hours. tex:\small\textstyle$TZC^{\circledR}tablet$ is an oral terazosin formulation that was intended to be developed as a generic formulation of tex:\small\textstyle$Hytrin^{\circledR}tablet$, an existing oral terazosin formulation in Korea. Therefore, we compared the pharmacokinetic characteristics and tested the bioequivalence of the two formulations in healthy Korean male subjects. Methods: The study was conducted as an open-labeled, randomized, 2-way crossover Latin square design in 18 healthy subjects. Subjects were separated into two groups. Subjects in one group were planned to be administered single doses of tex:\small\textstyle$Hytrin^{\circledR}tablets$ orally and one week later single doses of tex:\small\textstyle$TZC^{\circledR}tablets$. Subjects in another group were planned to be administered in opposite sequence in the same manner. Originally drugs in each period were to be administered in two divided days to 9 subjects each day, to guarantee the safety and well-being of subjects. But, actually, subjects were administered in three divided days to 7, 7 and 4 subjects respectively, due to private reasons of some subjects. Dosage administered was 1 mg as terazosin. Serial blood samples were collected till 48 hours after the drug administration. Plasma terazosin concentration were assayed by reversed phase HPLC using prazosin as internal standard. Pharmacokinetic parameters of the two formulations were analyzed by noncompartmental methods. We tested the sequence effect, period effect and differences of parameters between the two formulations by ANOVA. The pharmacokinetic characteristics of the two parameters were compared by 90% confidence intervals for ratios of tex:\small\textstyle$AUC_{0-{\infty}}$ and Cmax and the other pharmacokinetic parameters by student t-tests. Result : There was no difference in date groups when we analyzed the effect of dispersion of dates of drug administration to subjects using ANOVA, for p value was 0.1209. There were no differences between sequence, period and treatment groups, too. Total AUC of tex:\small\textstyle$TZC^{\circledR}tablets$ was tex:\small\textstyle$278.74{\pm}79.28\;ng\;{\times}\;hr/ml\;(mean{\pm}SD)$, and that of Hytrin tablet was tex:\small\textstyle$276.57{\pm}83.79$tex:\small\textstyle$C_{max}$ of tex:\small\textstyle$TZC^{\circledR}tablets$ was tex:\small\textstyle$26.61{\pm}7.16\;ng/ml\;(mean{\pm}SD)$, and that of tex:\small\textstyle$Hytrin^{\circledR}tablet$ was tex:\small\textstyle$26.54{\pm}8.46$. AUC ratio between two formulations in individual subjects was tex:\small\textstyle$1.019{\pm}0.138.\;t_{1/2}(terminal\;half-life)$tex:\small\textstyle$T_{max}$(time to maximum concentration), MRT(mean residence time) were similar between two formulations. The 90% confidence interval of total AUC difference between two tex:\small\textstyle$formulations(-17.86{\sim}22.20)$ was within the 20% of AUC of tex:\small\textstyle$Hytrin^{\circledR}tablet$, a tex:\small\textstyle$reference(-55.31{\sim}+51.31)$. The 90% confidence interval of tex:\small\textstyle$C_{max}$ difference between two tex:\small\textstyle$formulations(-2.44{\sim}2.66)$ was also within the 20% of tex:\small\textstyle$C_{max}$of tex:\small\textstyle$Hytrin^{\circledR}tablet(-5.31{\sim}+5.31)$. Therefore, tex:\small\textstyle$TZC^{\circledR}tablets$ and tex:\small\textstyle$Hytrin^{\circledR}tablet$ were bioequivalent. Conclusion : Bioequivalence study is a clinical trial with human beings as subjects. Therefore, we should conduct clinical trial with due regard to the safety and well-being of subjects. The dispersion of administration dates is likely to occur in actual clinical trial field. There were no statistically significant differences in date groups when analyzed by ANOVA test, and we could conclude that the administration of drugs in three divided days had no effect on the bioequivalence test results of ..