• The Korean Journal of Applied Statistics
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• v.29 no.2
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• pp.279-289
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• 2016

Bioequivalence trials based on higher order crossover designs have recently been conducted for highly variable drugs since the Ministry of Korea Food and Drug Safety (MFDS) added new regulations in 2013 to widen bioequivalence limits for highly variable drugs. However, a statistical discussion of higher order crossover designs have not been discussed yet. This research proposes the statistical inference of bioequivalence based on $3{\times}3$ crossover design and discusses it with the MFDS regulations. An illustrated example is also given.

• 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)

• Proceedings of the PSK Conference
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• 2003.04a
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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)

• Proceedings of the PSK Conference
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• 2003.10b
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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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• v.19 no.4
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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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• v.34 no.5
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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.

• Proceedings of the PSK Conference
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• 2002.10a
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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)

• YAKHAK HOEJI
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• v.34 no.5
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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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• v.6 no.4
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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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• v.29 no.2
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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.