The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and ...
The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and the analyte was quantified with UV detection at 251 nm. The calibration curve of the drug was linear over the range of 1-40ng/mL in human serum and the limit of quantification (LOQ) was 1 ng/mL. This analytical method was validated and shown to be specific, accurate, precise and reproducible. This method was applied to pharmacokinetic study of promethazine in Korean healthy volunteers following an oral administration of two 25 mg Himazin tablets (50 mg promethazine ${\cdot}$HCI) after overnight fasting. Serum samples were collected at given intervals over a 36-hour period (12 points) and pharmacokinetic parameters were determined from serum concentration-time profile using WinNonlin program. The estimated $AUC_{0__\infty}$, $AUC_{0_\infty}$, $C_{max}$, $T_{max}$ and $t_{1/2}$ of promethazine obtained from Korean healthy subjects were 103.84 ${\pm}$84.30 ng${\cdot}$hr/mL, 87.94${\pm}$81.02 ng${\cdot}$hr/mL, 13.43${\pm}$10.92 ng/mL, 2.00${\pm}$1.16 hr and 5.88${\pm}$3.47 hr, respectively.
The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and the analyte was quantified with UV detection at 251 nm. The calibration curve of the drug was linear over the range of 1-40ng/mL in human serum and the limit of quantification (LOQ) was 1 ng/mL. This analytical method was validated and shown to be specific, accurate, precise and reproducible. This method was applied to pharmacokinetic study of promethazine in Korean healthy volunteers following an oral administration of two 25 mg Himazin tablets (50 mg promethazine ${\cdot}$HCI) after overnight fasting. Serum samples were collected at given intervals over a 36-hour period (12 points) and pharmacokinetic parameters were determined from serum concentration-time profile using WinNonlin program. The estimated $AUC_{0__\infty}$, $AUC_{0_\infty}$, $C_{max}$, $T_{max}$ and $t_{1/2}$ of promethazine obtained from Korean healthy subjects were 103.84 ${\pm}$84.30 ng${\cdot}$hr/mL, 87.94${\pm}$81.02 ng${\cdot}$hr/mL, 13.43${\pm}$10.92 ng/mL, 2.00${\pm}$1.16 hr and 5.88${\pm}$3.47 hr, respectively.
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문제 정의
Therefore, the objective of this study was to examine the pharmacokinetics of promethazine in Korean healthy volunteers, using the modified HPLC analytical method. In this study, we validated a specific, accurate and reproducible HPLC method for the quantification of promethazine in human serum and applied the method to the pharmacokinetic study of promethazine following an oral dosing in Korean healthy vol- 니nteers.
제안 방법
Therefore, the objective of this study was to examine the pharmacokinetics of promethazine in Korean healthy volunteers, using the modified HPLC analytical method. In this study, we validated a specific, accurate and reproducible HPLC method for the quantification of promethazine in human serum and applied the method to the pharmacokinetic study of promethazine following an oral dosing in Korean healthy vol- 니nteers. Also, the results of this study in Korean could be used for the standard of bioequivalence test of promethazine.
Intra- and inter-day precision were determined by the analysis of the samples at four different concentrations of 1, 2, 10 and 20 ng/mL in five replicates within a day or during five consecutive days. The precision was calculated from the ratios of the standard deviation to the mean (coefficient of variation, C.
). The accuracy was examined by analyzing the samples at four different concentrations of 1, 2, 10 and 20 ng/mL during five consecutive days.
The validated analytical method was applied to measure serum levels of promethazine after a single oral administration of two 25 mg Himazin® tablets (50 mg promethazine - HCl) to 8 healthy male Korean volunteers (23-25 years, 63-85 kg). All the subjects were fasted overnight before drug administration and continued to be fasted for 4 hrs after the dosing.
대상 데이터
The HPLC system was composed of a LC-10AD pump, a SPD-10A UV detector and a C-R6A chromatopac data processor (Shimadzu, Tokyo, Japan). The HPLC analysis was carried out on a Capcell Pak CN column (5 μm particle size, 250 mm x 4.
성능/효과
The sensitivity was assessed by the limit of quantification (LOQ), the lowest concentration of the serum spiked with promethazine with a signal-to-noise ratio of > 5. The acceptable precision and accuracy limits of the LOQ were less than 20% C.V. and 20% bias (80 ~120% of the theoretical concentrations), respectively.
4 and pharmacokinetic parameters of promethaz-ine in Korean subjects were summarized in Table Ⅲ. The calculated AUCqe, AUCo.36, Cmax, Tmax and elimination halfe life (t1/2) of promethazine obtained from Korean subjects were 103.84 ± 84.30 ng - hr/mL, 87.94 ± 81.02 ng - hr/mL, 13.43 ±10.92 ng/mL, 2.00 ± 1.16 hr and 5.88 ± 3.47 hr, respectively.
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