• Biomolecules & Therapeutics
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• 제5권3호
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• pp.260-264
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• 1997

The bioequivalence of two nicotine patches was evaluated in 16 normal male volunteers (age 21 ~ 27 yrs) following single transdermal application. Test product was "Nicostop patch" made by Sam Yang Co. and reference product was "Nicotinell TTS patch" made by Korean Searle Ciba-Geigy Co. After nicotine patches were applied onto the inside of the forearm, blood was taken at predetermined time intervals and the nicotine concentration in plasma was determined with a sensitive GC method using NPD detector. AUC and Cm\ulcorner were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC and $C_{msx}$between two products were 5.47% and 2.70%, respectively. The powers (1-$\beta$) for AUC and $C_{max}$. were >90% and 88.76%, 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 "Nicostop patch" is bioequivalent to "Nicotinell TTS patch" . . .

• 한국임상약학회지
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• 제10권2호
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• pp.68-73
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• 2000

The bioequivalence of two omeprazole preparations was evaluated following their oral administration to 16 normal volunteers. The test product was 'Ulpro tablet' made by Boryung Pharmaceutical Co. and the reference was 'Losec capsule' made by Yuhan Corp. After one capsule or tablet containing 20 mg omeprazole was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was determined with an HPLC method. AUC and $C_{max}$ were determined and analyzed statistically for the evaluation of bioequivalence of the two products. The differences in AUC and $C_max$ between two products were $0.45\%\;and\;2.83\%$, respectively. The powers for AUC and $C_{max}\;were\;89.2\%\;and\;>90\%$, respectively. Confidence intervals were within $20\%$ for AVC and $C_{max}$All of these parameters met the criteria of KFDA for bioequivalence, indicating that 'Ulpro tablet' is bioequivalent to 'Losee capsule.'

• Archives of Pharmacal Research
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• 제18권4호
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• pp.237-242
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• 1995

For the vioequivalence study of two ceftriaxone injection formulations ($Rocephin{\circledR}$ ; Roche, and Triaxone ; Hanmi0, the HPLC analytical method for the analysis of ceftriaxone in plasma was used. Fourteen healthy volunteers completed the study and each subject were IM in jected signle doses (1 g) of the test and the reference formulations in a two-way crossover design with an one week drug free interval between doses. Following each administration, plasma concentrations of ceftrixone were monitored over a period of 24 h. Bioequivalence parameters $AUC_{24th}, {\;}T_{max}, {\;}C_{max}$ and MRT determined from the data obtained for the two formulations were examined by analyses of variance (ANOVA) and other criteria and tests for bioequivalence. Results of ANOVA and confidence limits of test/reference ratios of $AUC_{24th}, {\;}T_{max}, {\;}C_{max}$ and MRT, and statistical tests indicated the bioequivalence of the two formulations (i.e., test/reference ratio was within $100{\pm}20%$) except for $T_{max}$ The mean of $T_{max}$ showed only 6. 9% difference from the reference but the detection limit was 22.5% which is slightly over the 20% criteria. No pharmacokinetic parameters including Ka, Kel, Vd and Cl indicated significant difference in between the two fomulations. It was concluded that the data yielded fro the two cefriaxone formulations demonstrated that they were bioequivalent.

• 약학회지
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• 제33권4호
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• pp.229-236
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• 1989

Even though two different preparations are chemically equivalent, the variance of bioavailability differenciates the clinical effect of preparations, so that the preparations need to be evaluated by comparing bioavailability in vivo as well as chemical equivalence. In this study, bioequivalence tests of commercially available isoniazid tablets A, B, C and D (standard) were performed to give some guidelines to bioequivalence test. The bioavailability parameters obtained by drug administeration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance for a cross over design. Cross over design was employed with 8 healthy volunteers. The results were within 20% difference of mean value in the AUC, Cmax, Tmax and amount of urinary excretion (Au) between standard and isoniazid tablets. The results of ANOVA showed no significant differences for 'group or sequence', but almost not for 'between subjects'. The tablet. A, B and D were within 20 min, but tablet C was within 50 min. Tablet A was biologically equivalent in the Au. tablet B biologically equivalent in the Au and AUC. Tablet C was biologically equivalent in the Au. The relationship between the dissolution rate and Au was significant.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.88-89
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• 2003

In recent days, the bioequivalence(BE) study of domestic drugs on original drug are quite, activated in Korea. This BE study provide not only the bioequivalence of test and reference drug but also produce the population pharmacokinetic(PK) parameters in normal healthy Korean. The BE study can also make it possible to establish a PK/PD model of the drug when the additional pharmacodynamic(PD) data are available. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.246.1-246.1
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• 2003

Bioequivalence of two enalapril maleate tablets, formulation A and B, was evaluated according to the Korean Guidelines for Bioequivalence Test (KGBT 2001). Twenty healthy male volunteers (19∼27 years old) were randomly divided into two groups and a randomized 2x2 cross-over study was performed. Following oral administration of enalapril maleate tablets (20 mg dose), blood sample was taken at pre-determined time intervals and the concentrations of enalapril in plasma were determined using LC-MS. (omitted)

• 응용통계연구
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• 제18권1호
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• pp.159-171
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• 2005

최근 미국을 위시한 선진국에서 제제간의 생물학적 동등성을 판단하는 기준이 생체 이용률의 평균치를 비교하는 시험에서 분산까지 같이 고려하는 기준으로 바뀌고 있다. 처방성과 교차사용성을 의미하는 모집단과 개인 생물학적 동등성이 바로 그것이다. US FDA에서는 2 × 4 교차설계법을 활용해서 제제간의 생동성을 입증하는 것을 추천하고 있다. 현재 US FDA에서 제안하고 있는 모집단 생물학적 동등성 평가 방법은 통계적으로 문제점을 가지고 있어 최근 Lee, Shao & Chow(2002), Chow, Shao & Wang(2003), 그리고 McNally, Iyer & Mathew(2002)에 의해서 수정된 평가 방법들이 제안되고 있다. 본 연구 논문에서는 그동안 제제간의 생물학적 동등성 평가 설계법이였던 2×2 교차설계법을 이용해서 모집단 생물학적 동등성을 평가하는 방법을 논의하고 최근 제안된 방법들을 모의실험을 통해 비교하여 가장 적절한 방법론을 제안한다.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.117-123
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• 2010

Ibudilast, 3-isobutyryl-2-isopropyrazolo[1,5-a]pyridine, is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It preferentially inhibits PDE 3A, PDE4, PDE10 and PDE11 as well as a number of the other PDE families, albeit to a lesser extent. Ibudilast is used clinically to treat bronchial asthma and cerebrovascular disorders. Thes e clinical uses are based on the ability of ibudilast to inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The purpose of the present study was to evaluate the bioequivalence of two ibudilast capsules, Ketas capsule (Handok Pharmaceuticals Co., Ltd.) and Pinatos capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of ibudilast from the two ibudilast formulations was tested using KP Apparatus method with various dissolution media. Twenty six healthy male subjects, 23.31${\pm}$1.09 years in age and 70.45${\pm}$8.51 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single capsule containing 10 mg as ibudilast was orally administered, blood samples were taken at predetermined time intervals and the concentrations of ibudilast in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were 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, Ketas, were 6.99%, -2.48% and 9.93% 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 0.8791~log 1.1861 and log 0.8347~log 1.1199 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Pinatos capsule was bioequivalent to Ketas capsule.

• 한국임상약학회지
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• 제15권1호
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• pp.61-67
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• 2005

This study was designed to establish a strategy for the bioequivalence study of doxifluridine, an anticancer drug, in dogs instead of cancer patients. Although the results from animals may not occur in the same manner from human, those would be worth enough in terns of the bioequivalence. As for critically ill population such as cancer patients, bioequivalence studies in animals bring many advantages. Six healthy Beagle dogs were selected on the basis of hematology and blood chemistry test. After an over night fast, 200 mg of doxifluridine was orally administered, and blood was serially taken up to 12 hours. Plasma concentration of doxifluridine was measured using a newly validated bioanalytical method by a HPLC coupled tandem mass spectrometry. Time course of plasma doxifluridine concentration was analyzed with non-compartmental and compartmental approaches. Consequently, we represented hematology and blood chemistry database for the selection of healthy Beagle dogs, and suggested a sensitive and validated analytical method of doxifluridine, as well as a study design for the bioequivalence of doxifluridine in dogs.

• 약학회지
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• 제48권6호
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• pp.379-383
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• 2004

Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of chronic viral hepatitis B and drug-induced hepatitis through the inhibition of lipid peroxidation and c ovalent binding of drug metabolites to lipids of microsomes. The bioequivalence of two DDB products was evaluated according to the guidelines of KFDA. The test product was Hepaphil soft capsule(R) made by KMS Pharm. Co. Containing 3 mg DDB and the reference product was Nissel tablet(R) made by Taerim Pharm. Co. Containing 25 mg DDB. Twenty healthy male subjects, 25.4(22~30) years old and 66.7(54~77)kg, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets or two capsules were orally administered, blood was taken at predetermined time intervals and the concentration of DDB in plasma was determined using a validated HPLC method with UV detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.91~log1.00 and log 1.05~log 1.15, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hepaphil soft capsule is bioequivalent to Nissel tablet.