Various measures of rate and extent of absorption in bioequivalent study of norfloxacin tablet

Various measures of rate and extent of absorption were reported recently for bioequivalence study. Besides the widely used parameters, AUC(∞), C(max), LnAUC(∞) and LnC(max), partial AUC such as AUP(p), AUC1, AUC2 AUC3, combination parameters, C(max)/AUC(t(max)) and C(max)/t(max), were used. Other parameters using concentrations at specific times to the t(max) of the reference product were also applied. Comparison of the measurements between two norfloxacin tablet was selected as an example. Norfloxacin tablets were manufactured by two different pharmaceutical factories (Baccidal, Kyorin, Japan; Norfloxacin, Kingdom Taiwan, R.O.C.). A single oral 400 mg (4* 100 mg/tab) dose of Baccidal and Norfloxacin was administered in 12 healthy young Chinese males in a completely randomized double-blind cross-over design with a one-week wash-out period between each dose. Plasma samples were obtained before and after various appropriate intervals after dosing up to 24 hours. The plasma concentrations were then analyzed by a self-developed HPLC. The low detection limit of this HPLC method was 13 ng in plasma. The limit of quantitation was 40 ng/mL. Values for the area under the plasma concentration-time curve to time infinity (AUC(∞)), peak concentration (C(max)), time to peak concentration (t(max)), C(max)/AUC(tmax), C(max)/t(max), partial AUC, AUC1 2, and AUC to the t(max) (AUC(t(max))), volume of distribution and oral clearance were compared for each preparation. Log transformation of AUC(∞) and C(max) were also performed for comparison. Intra- and intersubject variations were checked by comparing apparent volume of distribution and oral clearance. All the parameters were not significantly different based on the results of ANOVA. By using power analysis and 90% confidence interval, we can conclude that Baccidal and Norfloxacin are bioequivalent. Among various measures of rate and extent of absorption, AUC12, C(max)/AUC(∞) had the same results with LnAUC(∞) and LnC(max). However, AUC(t(max)), C(max)/AUC(t(max)), and C(max)/t(max) had different results with the commonly used bioequivalent parameters. The meaning of each parameter is discussed in detail.