• Journal of Korean Society of Industrial and Systems Engineering
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• v.34 no.1
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• pp.67-73
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• 2011

Using the known result of the expected busy period for a controllable M/G/1 queueing model operating under the triadic Max (N, T, D) policy, its upper and lower bounds are derived to approximate its corresponding actual value. Both bounds are represented in terms of the expected busy periods for the dyadic Min (N, T), Min (N, D) and Min (T, D) and simple N, T and D operating policies. All three input variables N, T and D are equally contributed to construct such bounds for better estimation.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.185-191
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• 1998

A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

• Journal of Pharmaceutical Investigation
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• v.39 no.6
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• pp.451-456
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• 2009

The purpose of the present study was to evaluate the bioequivalence of two ciprofloxacin tablets, Ciprobay (Bayer Korea Ltd.) and Rofcin (Binex Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The release of ciprofloxacin from the two ciprofloxacin tablets in vitro was tested using KP XIII Apparatus I method with dissolution media (0.01 M HCl). The dissolution profiles of two ciprofloxacin tablets were very similar at dissolution media. Twenty four healthy male volunteers were divided into two groups and a randomized 2$2{\times}2$2 cross-over study was employed. After one tablet (250 mg ciprofloxacin) was orally administrated, blood was taken and the concentrations of ciprofloxacin in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two ciprofloxacin tablets based on the Ciprobay were -0.63%, 3.98% and -9.23%, respectively. There were no sequence effects between two tablets in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25)(e.g., log(0.9520)~log(1.0523) and log(0.9689)~log(1.1663) for $AUC_1\;and\;C_{max}$, respectively). Thus, Rofcin tablet was bioequivalent to Ciprobay tablet.

• Korean Journal of Clinical Pharmacy
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• v.7 no.2
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• pp.67-72
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• 1997

The bioequivalence of two lomefloxacin tablets was evaluated in 16 normal male volunteers (age $21\sim30$ yrs) following oral administration. Test product was 'Lomaxacin tablet' made by Kolon Pharmaceutical Co. and reference product was 'Maxaquin tablet' made by Searle Ciba-Geigy Korea Co. After one tablet containing 400 mg of lomefloxacin was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was determined with an HPLC method using fluorescence detector. AUC, $C_{max},\;and\;T_{max}$ were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, $C_{max},\;and\;T_{max}$ between two products were $0.90\%,\;1.09\%,\;and\;2.44\%$, respectively. The powers (1-${\beta}$) for AUC, $C_{max},\;and\;T_{max}\;were\;>95\%,\;>95\%,\;and\;93.8\%$, respectively Detectable differences $(\Delta)$ and confidence intervals were all less than $20\%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that 'Lomaxacin tablet' is bioequivalent to 'Maxaquin tablet'.

• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.67-72
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• 1994

Bioequivalence (BE) test of biphenyl dimethyl dicarboxylate (DDB) tablets was performed. Normal healthy male volunteers (n = 20) were randomly divided into 2 groups, and reference $(Nissel{\circledR})$ and test $(Livital{\circledR})$ tablets of DDB $(25mg{\times}8\;Tab.\;= \;200\;mg)$ were given orally by balanced two-period cross-over design. The serum concentration was determined by high performance liquid chromatography. The pharmacokinetic parameters, AUC, $C_{max}$, and $T_{max}$ obtained after drug administration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance (ANOVA) for cross-over design. The results were within 20% differences of mean value in AUC, $C_{max}$, and $T_{max}$ between reference and test tablets. The results of ANOVA showed no significant differences for "between group or subject" and "period". The test tablet was bioequivalent with the reference tablet in the AUC, $C_{max}$, and $T_{max}$.

• Archives of Pharmacal Research
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• v.13 no.2
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• pp.180-186
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• 1990

A bioequivalence study of ranitidine tablets was conducted according to the Korean Guidine for the Bioequivalence Test using twelve healthy male subjects. The plasma concentration-timecurves of ranitidine from the test and reference tablets showed profound multiple peak phenomenon in each subject as reported earlier. However, the area under the plasma concentration-time curve (AUC) and the maximum ploasma concentration at the first peak ($C_{max1}$) of the two preparations was proven to be equal when analyzed satistically according to the criteria of the guidline;i. e., statistical power (1-$\beta$)was calculated to be over 0.8 under the condition of $\alpha$ = 5% and $\Delta$(minimum detectable difference) = 20%, and the confidence interval of the difference in AUC at 95% confidence level was in the range of $\pm$ 20%, which statisfied the criteria of bioequivalence. Equivalence of the peak concentration of ranitidine at the second peak ($C_{max2}$), and the time to reach the first ($T_{max1}$) and second verify the bioequivalence of $c_{max2}$ , $T_{max1}$ and $T_{max2}$ between the two tablets. However, we conclude that the test and reference tablets are bioequivalent taking the therapeutic characteristics of the ranitidine preparations into consideration.

• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.361-365
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• 1999

The bioequivalence of 'Bearcef tablet' (Daewoong Pharmaceutical Co.), containing 250 mg cefuroxime (as cefuroxime axetil), in reference to 'Zinnat tablet' (GlaxoWellcome Korea Co.) was evaluated in 16 normal volunteers $(age\; 21{\sim}29\;yrs)$ following the oral administration. After one tablet was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was quantitated with an HPLC method. AUC, $C_{max}$ and $T_{max}$ were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, $C_{max}$ and $T_{max}$ between two products were 6.92%,3.49% and 5.26%, respectively. The powers for AUC, $C_{max}$ and $T_{max}$ were >90%, >90% and 89.0%, respectively. Confiderice intervals for these parameters were all within ${\pm}20%$. Judging based on the above results, 'Bearcef tablet' is regarded to be bioequivalent to 'Zinnat tablet'.

• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.44-48
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• 1999

The bioequivalence of two aceclofenac tablets was evaluated in 14 normal volunteers (age $21\sim29$ yrs) following oral administration. The test product was 'Apental tablet' made by Asia Pharmaceutical Co. and the reference was 'Airtal tablet' made by Daewoong Pharmaceutical Co. After one tablet containing 100 mg aceclofenac was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was quantitated with an HPLC method. AUC, $C_{max}\;and\;T_{max}$ were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, $C_{max}\;and\;T_{max}$ between two products were $4.23\%,\;2.15\%\;and\;0\%$, respectively. The powers for AUC,$\;C_{max}\;and\;T_{max}\;were\;>90\%,\;>90\%\;and\;85.8\%$, respectively. Confidence intervals were within $\pm20\%$ for three parameters. All of these parameters met the criteria of KFDA for bioequivalence, indicating that 'Apental tablet' is bioequivalent to "Airtal tablet".(Kor. J. Clin. Pharm. 1999; 9(1): 44-48)

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.215-221
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• 2002

Cephradine is a first generation cephalosporin and has broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms, through inhibition of bacterial cell wall synthesis. Cephradine is useful for treatment of infections of the urinary and respiratory tract, skin and soft tissues. The purpose of the present study was to evaluate the bioequivalence of two cephradine capsules, Cefradine Yuhan (YuHan Corporation) and Broadcef (Ilsung Pharmaceuticals Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cephradine release from the two cephradine capsules in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $23.10{\pm}2.90$ years in age and $67.69{\pm}8.04\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 500 mg as cephradine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephradine in serum were determined using HPLC method with UV detector. The dissolution profiles of two cephradine capsules were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AVC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Cefradine Yuhan were -2.87%, -0.96% and -4.85%, respectively. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of 1og(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.02)\;and\;log(0.88){\sim}log(1.13)\;for \;AVC_t\;and\;C_{max},\;respectively)$. The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g., \;-17.54{\sim}7.78\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Broadcef capsule is bioequivalent to Cefradine Yuhan capsule.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.127-133
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• 2002

Levosulpiride is the 1evo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic $D_2$ receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequiva1ence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight normal male volunteers, $23.82{\pm}3.26$ years in age and $69.13{\pm}8.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride tablets were very 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 $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.07)\;and\;log(0.90){\sim}log(1.14)\;for\;AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g.,\;-19.47{\sim}16.20\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.