• 응용통계연구
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• 제29권2호
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• pp.279-289
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• 2016

최근 식품의약품안전처는 의약품동등성시험기준에 고변동성 제제의 생물학적 동등성(생동성) 평가 기준을 넓혀주는 새로운 규정을 추가하면서 고차 교차설계법을 활용하여 생동성 평가를 하는 논의가 확대되고 있다. 확장된 생동성 기준을 적용하기 위해서는 3기간 이상의 교차설계법이 적용되어야 하지만 아직 관련된 논의가 많이 이루어지지 않고 있다. 본 연구에서는 $3{\times}3$ 교차설계법에 기초한 생동성 평가의 통계적 추론과정을 제시하고 논의한다. 또한 사례를 통해 $3{\times}3$ 교차설계법을 활용한 생동성 평가를 식품의약품안전처 의약품동등성시험기준에 따라 진행하고 그 의미를 논의한다.

• 한국임상약학회지
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• 제9권1호
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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)

• 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)

• Journal of Pharmaceutical Investigation
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• 제19권4호
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• pp.191-194
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• 1989

Bioequivalence test of $Asthcontin^{\circledR}$ tablet, a commercial slow-release theophylline (TP) dosage form, was performed using $Slo-bid^{\circledR}$ capsule as the reference. Since it has been confirmed that the saliva concentration of TP is closely correlated with the plasma concentration in man, the area under the saliva concentration-time curve was used as a bioavailability parameter. The statistical analysis showed that the two dosage forms are equivalent in bioavailability estimating from the saliva concentration. The results supported that the use of soliva as a test sample provides simple and easy techniques for bioequivalence tests of TP-containing dosage forms.

• Journal of Pharmaceutical Investigation
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• 제34권5호
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• pp.379-383
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• 2004

Statistical interpretations in a bioequivalence trial are considered and studied when the missing observations occurred in $2\;{\times}\;2$ crossover experiment. Patel (1985) suggested the approximate test procedures for carryover effect and drug effect in $2\;{\times}\;2$ crossover design when some of data are missing in the second period. A modified Patel method is newly proposed to the bioequivalence trial and it is compared with the current method through the simulation study.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.411.3-412
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• 2002

On the basis of recognizing that physicochemical properties (lipophilic/hydrophilic), intestinal absorption clearance and pharmacokinetic characteristics of drug are the fundamental parameters controlling the rate and the extent of drug absorption, the biopharmaceutics classification system for the correlation between drug lipid- solubility and intestinal absorption clearance is proposed. (omitted)

• 약학회지
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• 제34권5호
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• pp.334-340
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• 1990

The bioequivalence of Mandol and Mancef (cefamondole nafate injection preparation) was investigated for 8 healthy human volunteers. Cefamandole nafate hydrolysis to cefamandole base in the blood and shows antibacterial activity. As the rate of the hydrolysis can be varied according to the buffer used in the preparation, the bioequivalence of cefamandole nafate I.V. was studied. A new HPLC method, the column switching technique, was developed and used for the simultaneous determination of cefamandole and cefamandole nafate in the plasma and in the urine. There were no statistically significant difference in between Mandol and Mancef for the parameters of AUC and Cp 0.25 hr even through the power of the test was not enough.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.417-422
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• 1998

Loxoprofen sodium (sodium 2-[4-(2-oxocyclopentylmethyl)phenyl] propionate dehydrate) is a nonsteroidal antiinflammatory drug of $\alpha$-phenyl propionic acid derivative. To test the bioequivalence of loxoprofen, the pharmacokinetic parameters of new preparation of loxoprofen, LENOX was compared with LOXONIN as a reference drug. Fourteen healthy volunteers were entered to the stydy (Yonsei University College of Medicine, Severance Hospital IRB approval No. 9608). They were administered 60 mg of loxoprofen in 2$\times$2 cross-over design. There was one week of drug-free interval between doses. The blood sample was taken on schedule up to 8 hours, and the plasma concentration loxoprofen was measured by reverse phase high-performance liquid chromatography (HPLC) with UV-detector. There were no significant difference between two preparations when AUC, Cmax, and Tmax were compared by ANOVA. The mean differences of AUC, Cmax, and Tmax were within 20% of the reference drug: the values were 2.22,5.61, and 12.50%, respectively. The confidence limits of AUC and Cmax but not Tmax satisfied the bioequivalence criteria. These results suggest that the tested LENOX is bioequivalent to the reference drug.

• Journal of the Korean Statistical Society
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• 제29권2호
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• pp.219-229
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• 2000

Oh et al.(1999) 3$\times$2 crossover design for assessing bioequivalence when two new generic drug formulations and innovator are simultaneously considered. This design is not only more efficient than 3$\times$3 one, proposed by Lee et al.(1998), in practical sense, but also more ethical in medical sense. However, the general statistical methods are not directly applicable to both designs when subjects are dropped out in the experiment, even though it is always possible in bioavailability and bioequivalence studies because of some administrative and economic reasons. In this research we propose an inference to drug effects when subjects are dropped out in the planed-for 3$\times$3 and 3$\times$2 crossover experiments. An example is given for illustration.