• The Korean Journal of Applied Statistics
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• v.18 no.1
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• pp.159-171
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• 2005

The US Food and Drug Administration(FDA) recommends that population bioequivalence and individual bioequivalence would be assessed to address the prescribability and switchability between a brand-name drug and its new formulation or generic copy in its 2001 guidance document. The test for population bioequivalence in the latest FDA guidance is recommended in 2 x 4 crossover design, but it turns out to be very conservative. Recently Lee, Shao & Chow(2002), Chow, Shao & Wang(2003) and McNally, Iyer & Mathew(2002) proposed new statistical methods for assessing population bioequivalence between drugs to correct the biasness of current FDA method. Since 2 x 2 crossover experiment is most welcomed design in bioequivalence testing, we adopt their methods to 2 x 2 crossover designs and compare their methodologies with FDA one through the simulation study.

• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.217-219
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• 2009

There are several approaches to calculate a sample size for bioequivalence test. Among these approaches, sample sizes determination based on Schuirmann's two one-sided tests procedures has been used most popularly in case of 2${\times}$2 bioequivalence study. Here we proposed simple sample size table for conventional 2${\times}$2 bioequivalence test based on Schuirmann's two one-sided tests in accordance with Korean Guidelines for Bioequivalence Test. This table will allow researchers with a little statistical background to calculate the sample size for bioequivalence with easy process.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.419-425
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• 2004

The purpose of the present study was to evaluate the bioequivalence of two propiverine hydrochloride tablets, BUP-4 (Jeil Pharm. Co., Ltd.) and Kuhnil Propiverine Hydrochloride (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The propiverine release from the two propiverine hydrochloride formulations in vitro was tested using KP VIII Apparatus II method with a variety of dissolution media (pH 1.2, 4.0, 6.8 buffer solutions, water and blend of polysorbate 80 into pH 6.8). Twenty six healthy male subjects, $23.73{\pm}2.79$ years in age and $67.04{\pm}7.93\;kg$ in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross-over study was employed. After one tablet containing 20 mg as propiverine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of propiverine in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t,\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the BUP-4 were 0.17%, 7.98% and 4.55% for $AUC_t,\;C_{max}\;and\;T_{max}$. respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.88){\sim}log(1.l2)\;and\;log(0.90){\sim}log(1.l5)\;for\;AUC_t\;and\;C_{max},\;respectively)$. Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kuhnil Propiverine Hydrochloride tablet was bioequivalent to BUP-4 tablet.

• Proceedings of the Korean Statistical Society Conference
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• 2002.05a
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• pp.67-72
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• 2002

A Bayesian testing procedure is proposed for assessment of bioequivalence in both mean and variance which ensures population bioequivalence under normality assumption. We derive the joint posterior distribution of the means and variances in a standard 2 ${\times}$ 2 crossover experimental design and propose a Bayesian testing procedure for bioequivalence based on a Markov chain Monte Carlo methods. The proposed method is applied to a real data set.

• The Korean Journal of Applied Statistics
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• v.24 no.6
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• pp.1095-1102
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• 2011

The classical two-period, two-sequence crossover design is no longer sufficient to assess various demands in a bioequivalence study. For instance, to estimate the within-subject and between-subject variances of test and reference formulations separately, it is necessary to use a replicate design in which each subject receives at least the reference formulation in two periods. Several designs were studied to satisfy the demands. It is provided a unified Bayesian approach applicable to those study designs. The benefit of the method in the bioequivalence study is discussed.

• Communications for Statistical Applications and Methods
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• v.8 no.2
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• pp.443-452
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• 2001

The 2x3 cross-over design is proposed for the bioequivalence of two test drug formulations with a reference drug formulation. Oh et al.(1999) and Park et al.(1998) derived 3x2 cross-over design and discussed its benefits, since the 3x3 cross-over design may not be of practical design. We discuss the statistical issues for2x3 cross-over design and show its statistical properties. Bioequivalence problem in 2x3 cross-over design is considered statistically and an illustrated example is given.

• Journal of the Korean Data and Information Science Society
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• v.18 no.2
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• pp.365-373
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• 2007

Sample size determination plays an important role in designing a bioequivalence trial. Formulae of sample sizes based on Schuirmann's two one-sided tests procedures are given for bioequivalence studies with the $2{\times}2$ crossover design and two-sample parallel design. A practical discussion for the relationship among these formulae is given.

• Journal of the Korean Data and Information Science Society
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• v.17 no.1
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• pp.245-257
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• 2006

A modified Anderson and Hauck(1983) test for analyzing a two-sequence two-period crossover design in bioequivalence trials is proposed when some observations at the second period are missing. It is based on the maximum likelihood estimators of average bioequivalence model and designed for handling missing at random(MAR) situation. The performance of the proposed test is compared to other tests using Monte Carlo simulations.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.39-44
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two cefaclor capsules, Ceclor (Lilly Korea Co., Ltd.) and Kyongbocefaclor (Kyongbo Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of cefaclor from the two cefaclor formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four healthy male subjects, $22.96{\pm}1.52$ years in age and $67.03{\pm}7.90$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After one capsule containing 250 mg of cefaclor was orally administered, blood was taken at predetermined time intervals and the concentrations of cefaclor in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Ceclor, were -1.90%, 2.68% and -7.60% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g.,\;log0.91{\sim}log\;1.06\;and\;log0.92{\sim}log\;1.18\;for\;AUC_t\;and\;C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kyongbocefaclor capsule was bioequivalent to Ceclor capsule.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.405-411
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• 2006

Epinastine is an antiallergic drug effective for bronchial asthma, allergic rhinitis, urticaria and dermatitis. Epinastine is topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. The purpose of the present study was to evaluate the bioequivalence of two epinastine hydrochloride tablets, Alesion Tablet (Boehringer Ingelheim Korea Ltd.) and S-napine tablet 10 mg(Sam Chun Dang Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration(KFDA). The release of epinastine from the two epinastine formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media(pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.35{\pm}1.57$ years in age and $66.29{\pm}10.61kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 20 mg as epinastine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of epinastine in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t.\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Alesion tablet, were 1.50, 1.46 and -13.48% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25(e.g., log 0.95$\sim$log 1.12 and log 0.93$\sim$log 1.10 for $AUC_t\;and\;C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating S-napine tablet 10 mg was bioequivalent to Alesion tablet.