The purpose of this study is to investigate the bioequivalence of two haloperidol 5 mg tablets, Myung In haloperidol (Myung In Pharm. Co., Ltd., test drug) and $Peridol^{R}$(Whanin Pharm. Co., Ltd., reference drug), and also to estimate the pharmacokinetic parameters of haloperidol in Kor...
The purpose of this study is to investigate the bioequivalence of two haloperidol 5 mg tablets, Myung In haloperidol (Myung In Pharm. Co., Ltd., test drug) and $Peridol^{R}$(Whanin Pharm. Co., Ltd., reference drug), and also to estimate the pharmacokinetic parameters of haloperidol in Korean volunteers. The bioavailability and pharmacokinetics of haloperidol tablets were examined on 24 healthy volunteers who received a single oral dose of each preparation in the fasting state in a randomized balanced 2 way crossover design. After an oral dosing, blood samples were collected for a period of 60 h. Plasma concentrations of haloperidol were determined using a liquid chromatographic electrospray mass spectrometric (LC-MS) method. The pharmacokinetic parameters were calculated with noncompartmental pharmacokinetic analysis. The geometric means of $AUC_{0-60h} and C_{max}$ between test and reference formulations were $17.21\pm8.26 ng\cdot/mL vs 17.31\pm13.24 ng\cdot/mL and 0.87\pm0.74 ng/mL vs 0.85\pm0.62 ng/mL$. respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-60h} and C_{max} were log0.9677{\sim}log1.1201 and log0.8208{\sim}log1.1981$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The geometric means of other pharmacokinetic parameters ($AUC_{inf}. t_{1/2}, V_{d}/F, and CL/F$) between test drug and reference drug were $21.75\pm8.50 ng{\cdot}h/mL vs 21.77\pm15.63 ng{\cdot}h/mL, 29.87\pm8.25 h vs 29.60\pm7.56 h, 11.51\pm5.45 L vs 12.90\pm6.12 L and 0.26\pm0.09 L/h vs 0.31\pm0.17 L/h$, respectively. These observations indicate that the two formulation for haloperidol was bioequivalent and, thus, may be clinically interchangeable.
The purpose of this study is to investigate the bioequivalence of two haloperidol 5 mg tablets, Myung In haloperidol (Myung In Pharm. Co., Ltd., test drug) and $Peridol^{R}$(Whanin Pharm. Co., Ltd., reference drug), and also to estimate the pharmacokinetic parameters of haloperidol in Korean volunteers. The bioavailability and pharmacokinetics of haloperidol tablets were examined on 24 healthy volunteers who received a single oral dose of each preparation in the fasting state in a randomized balanced 2 way crossover design. After an oral dosing, blood samples were collected for a period of 60 h. Plasma concentrations of haloperidol were determined using a liquid chromatographic electrospray mass spectrometric (LC-MS) method. The pharmacokinetic parameters were calculated with noncompartmental pharmacokinetic analysis. The geometric means of $AUC_{0-60h} and C_{max}$ between test and reference formulations were $17.21\pm8.26 ng\cdot/mL vs 17.31\pm13.24 ng\cdot/mL and 0.87\pm0.74 ng/mL vs 0.85\pm0.62 ng/mL$. respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-60h} and C_{max} were log0.9677{\sim}log1.1201 and log0.8208{\sim}log1.1981$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The geometric means of other pharmacokinetic parameters ($AUC_{inf}. t_{1/2}, V_{d}/F, and CL/F$) between test drug and reference drug were $21.75\pm8.50 ng{\cdot}h/mL vs 21.77\pm15.63 ng{\cdot}h/mL, 29.87\pm8.25 h vs 29.60\pm7.56 h, 11.51\pm5.45 L vs 12.90\pm6.12 L and 0.26\pm0.09 L/h vs 0.31\pm0.17 L/h$, respectively. These observations indicate that the two formulation for haloperidol was bioequivalent and, thus, may be clinically interchangeable.
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제안 방법
The administration of two haloperidol preparations to the subjects followed a balanced two-way crossover design with a week drug free interval between the two administrations. All subject were fasted for at least 10 h prior to the timing of the dose.
The p나!pose of this study was to determine the pharmacokinetic parameters of two brands of haloperidol 5 mg tablets and then to compare these parameters statistically to evaluate the bioeq니ivalence of the two preparations. Myung In 너aloperid이 (Myung In Pharm.
대상 데이터
In this bioequivalence study, 24 health volunteers were participated (ag으 23.3 ±1.65 years, weight: 63.6 ± 8.65 kg, height: 170.8 ±7.26 cm). All subjects w이"e elected after completing a thorough history and physical examination, and after a normal laboratory examination consisting of hematology, serum chemistry and urinalysis.
데이터처리
25). All statistical comparisons were carried out using K-BE test program (KFDA, Korea).
For the purpose of bioequivalence analysis AUG and Cmax were considered as primary variables. Bio으q니 fence was assessed by means of an analysis of variance (ANOVA) for crossover design and calculating standard 90% confidence intervals of the ratio test/reference (T/R). AUCt and Cmax ANOVA were performed using logarithmically transformed AUCt and Cmax.
성능/효과
1-5 ng/mL, respectively. Detection limits were 0.1 ng/mL Correlation coefficients for calibration were better than 0.999, and intraday and interday variability were less than 10%.
No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was property performed. Significant Ftest values were found between the subjects and subjects nested sequence (SEQ) for AUC60h and Cmax, indicating a substantial inter-subject variation in the pharmacokinetics of haloperidol from the two formulations (Table Ⅲ). No significant period effect in AUC60h and Cmax was detected in this study.
AUCt and Cmax ANOVA were performed using logarithmically transformed AUCt and Cmax. The formulations were considered bioequivalent if the difference between two compared parameters was found not statistically significant (i.e., P>0.05) and 90% confidence interv기s for these parameters fell within 80 ± 125% (Iog0.8-1.25). All statistical comparisons were carried out using K-BE test program (KFDA, Korea).
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