Jae-Hwan Rew

Bioequivalence of Mepiril Tablet to Amaryl Tablet (Glimepiride 2 mg) by Liquid Chromatography/Electrospray Tandem Mass Spectrometry

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, Amaryl tablet (Handok & Aventis Korea, reference drug) and Mepiril tablet (Myungmoon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (glibenclamide) to human plasma, plasma samples were extracted using 1mL of methyl tertiary butyl ether. Compounds extracted were analyzed by reverse-phase HPLC with multiple reaction monitoring (MRM) mode analyte detection. This method for determination glimepiride proved accurate and reproducible, with a limit of quantitation of 2 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the glimepiride dose of 2 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of glimepiride were monitored by a LC-MS/MS for over a period of 12 hr after the administration. (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the ratio and the ratio for Amaryl/Mepiril were log 0.9583-log 1.1357 and log 1.0570-log 1.2376, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Taken together, our study demonstrated the bioequivalence of Amaryl and Mepiril with respect to the rate and extent of absorption.

Bioequivalence Evaluation of Two brands of Cetirizine HCl 10 mg Tablets (Zyrix and Zyrtec) in Healthy Male Volunteers

The purpose of the present study was to evaluate the bioequivalence of two cetirizine HCl tablets, Zyrtec tablet (UCB Pharm. Co., Ltd. Korea, reference product) and Zyrix tablet (Kukje Pharm. Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (diazepam), plasma samples were extracted using 1 mL of dichloromethane. Compounds extracted were analyzed by reverse-phase HPLC with ultra-violet detector. This method for determination cetirizine is proved accurate and reproducible with a limit of quantitation of 10 ng/mL in male plasma. Twenty-four healthy male Korean volunteers received each medicine at the cetirizine HCl dose of 10 mg in a crossover study. There was a one-week wash out period between the doses. Plasma concentrations of cetirizine were monitored for over a period of 24 hr after the administration. AUC (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC and . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25 . The major parameters, AUC and met the criteria of KFDA for bioequivalence indicating that Zyrix tablet is bioequivalent to Zyrtec tablet.

Bioequivalence of A-PINE Tablet to SKAD Tablet (Amlodipine Maleate 6.42 mg)

The purpose of this study was to evaluate the bioequivalence of two amlodipine maleate tablets, SKAD tablet (SK Pharma. Co., Ltd., Seoul, Korea, reference drug) and A-PINE tablet (Daewon Pharm. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male volunteers, years in age and kg in body weight, were divided into two groups and a randomized crossover study was employed. After a tablet containing 6.42 mg of amlodipine maleate was orally administrated, blood was taken at predetermined time intervals over a period of 144 hr and concentrations of amlodipine in plasma were monitored using LC-MS/MS. Pharmacokinetic parameters such as (the area under the plasma concentration-time curve from time zero to 144 hr), (maximum plasma drug concentration) and (time to reach ) were calculated and analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed and , and untransformed . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the ratio and the ratio for A-PINE/SKAD were and , respectively. Since these values were within the acceptable bioequivalence intervals of , recommended by KFDA, it was concluded that A-PINE tablet was bioequivalent to SKAD tablet, in terms of both rate and extent of absorption.

Bioequivalence of Losartan TM Tablet to Cozzar TM Tablet (Losartan Kalium 50 mg)

The purpose of the present study was to evaluate the bioequivalence of two losartan tablets, tablet (MSD Korea. Co., Ltd., Seoul, Korea, reference drug) and tablet (DaeWon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the losartan kalium dose of 100 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of losartan were monitored by an LC-MS/MS for over a period of 12 hr after the administration. (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the ratio and the ratio for were , respectively. These values were within the acceptable bioequivalence intervals of . Taken together, our study demonstrated the bioequivalence of and with respect to the rate and extent of absorption.

Bioequivalence of FLUTAL Tablet to SOMALGEN Tablet (Talniflumate 370 mg)

The purpose of the present study was to evaluate the bioequivalence of two talniflumate tablets, SOMALGEN tablet (Kun Wha Pharm. Co., Ltd., Seoul, Korea, reference drug) and FLUTAL tablet (Kukje Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the talniflumate dose of 740 mg in a crossover study. There was a one-week washout period between the doses. Plasma concentrations of niflumic acid were monitored by an HPLC-UV for over a period of 14 hr after the administration. (the area under the plasma concentration-time curve from time zero to 14 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed , and untransformed . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the , ratio and the ratio for SOMALGEN/FLUTAL were and , respectively. These values were within the acceptable bioequivalence intervals of . Taken together, our study demonstrated the bioequivalence of SOMALGEN and FLUTAL with respect to the rate and extent of absorption.

Bioequivalence of Yutanal ® Capsule to Harnal ® Capsule (Tamsulosin HCl 0.2 mg)

The purpose of the present study was to evaluate the bioequivalence of tamsulosin HCl capsule, (Jeil Korea Ltd.) and (Kukje Korea Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, year in age and kg in body weight, were divided into two groups and a randomized cross-over study was employed. After one capsule containing 0.2 mg of tamsulosin HCl were orally administered, blood was taken at predetermined time intervals and concentrations of tamsulosin in plasma were determined using LC-MS/MS. Pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed , and untransformed . There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log0.8 to log1.25 (e.g., and for , and , respectively). The major parameters, , and , met the criteria of KFDA for bioequivalence indicating that capsule is bioequivalent to capsule.

Bioequivalence of Favid Tablet to Tarivid Tablet (Ofloxacin 100 mg)

The purpose of the present study was designed to evaluate the bioequivalence of two ofloxacin tablets, Tarivid (Jeil Pharm. Co., Ltd.) and Favid (ILHWA Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, year in age and kg in body weight, were divided into two groups and a randomized cross-over study was employed. After four tablets containing 100 mg of ofloxacin were orally administered, blood was taken at predetermined time intervals and concentrations of ofloxacin in plasma were determined using HPLC. Pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed and and untransformed . There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log 0.8 to log 1.25 (e.g., , respectively). The major parameters, , and , met the criteria of KDFA for bioequivalence indicating that Favid tablet is bioequivalent to Tarivid tablet.

Bioequivalence of Benipine Tablet to Codipine Tablet (Benidipine Hydrochloride 4 mg)

The purpose of the present study was designed to evaluate the bioequivalence of two benidipine hydrochloride tablets, Codipine (Youngjin Pharm. Co., Ltd.) and Benipine (Myungmoon Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, year in age and kg in body weight, were divided into two groups and a randomized cross-over study was employed. After two tablets containing 4 mg of benidipine hydrochloride were orally administered, blood was taken at predetermined time intervals and concentrations of benidipine in plasma were determined using LC-MS/MS. Pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed , and . There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log0.8 to log1.25 for , and respectively). The major parameters, and , met the criteria of KDFA for bioequivalence indicating that Benipine tablet is bioequivalent to Codipine tablet.

Validation of a Simple HPLC Method for Determination of Nicardipine in Human Plasma and Its Application to Single-dose Pharmacokinetics

A simple HPLC method with ultraviolet detection of nicardipine in human plasma was developed and validated. After drug extraction with solid phase extraction (SPE) method, chromatographic separation of nicardipine in plasma was achieved at with a column and acetonitrile-0.02% phosphate buffer mixture (with 0.02% triethylamine, final pH 7.0), as mobile phase. Quantitative determination was performed by ultraviolet detection at 254 nm. The method was specific and validated with a limit of quantification of 5 ng/mL. The intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of the method was demonstrated by analysis of plasma after oral administration of a single 40 mg dose to 8 healthy subjects. From the plasma nicardipine concentration versus time curves, the mean , was and of reached 1.5 hr after administration. The mean biological half-life of nicardipine was . Based on the results, this simple and validated assay method could readily be used in any pharmacokinetic or bioequivalence studies using human.

Validation of a Simple HPLC Method for Determination of Ciprofloxacin Hydrochloride in Human Plasma

A simple HPLC method with ultraviolet detection of ciprofloxacin in human plasma was developed and validated. After protein precipitation with trichloroacetic acid, chromatographic separation of ciprofloxacin in plasma was achieved at with a column and methanol-phosphate mixture (pH 2.5), as mobile phase. Quantitative determination was performed by ultraviolet detection at 278 nm. The method was specific and validated with a limit of quantification of 100 ng/ml. The intra- and inter-day coefficients of variation were between 1.67% and 10.55% and accuracy between 92.01 % and 106.09%. The method has been successfully applied in a bioavailability study of 250 mg ciprofloxacin hydrochloride tablet.