• Journal of Korean Medicine Rehabilitation
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• v.29 no.4
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• pp.101-108
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• 2019

Objectives The purpose of this study is to evaluate the safety of Gunghatang tablet in healthy male volunteers. Methods Single center pharmacokinetics study was carried out in healthy male volunteers. Through the laboratory test, vital sign and adverse event data, safety evaluation was conducted. Total 15 of 16 subjects who met the inclusion criteria were enrolled and three subjects were allocated to waiting group. 12 subjects were allocated by serial number according to registration order. Subjects took the maximum daily dose of the tablet on the second day of hospitalization. For the evaluation of safety, blood samples were collected and vital sign were checked 4 times (screening, before administration, after administration and follow up period) during the trial. All adverse events were recorded and summarized as frequency and percentage. All continuous data were summarized as mean and standard deviation. For comparison of variables between before administration and after administration, data were analyzed by paired T-test or Wilcoxon signed rank test (p<0.05). Results As a result of all data related to vital sign and laboratory test in both group, there were no significant differences associated with the clinical trial drug between pre and post administration. And there was no adverse event associated with the clinical trial drug. Conclusions Gunghatang tablet were found to be safe for healthy male volunteers.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.289-295
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• 1998

The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca $l_{R}$ tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi $l_{R}$ tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4$\pm$ 10.24% (mean$\pm$ 5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-$_{8 hr}$) (22.8$\pm$5.90 vs 22.2$\pm$6.10 ng . hr/ml), maximum plasma concentration ( $C_{max}$) (10.0$\pm$2.85 vs 9.3$\pm$3.28 ng/ml) and time to reach maximum plasma concentration ( $T_{max}$) (1.2$\pm$0.31 vs 1.3 $\pm$0.47 hr). The differences of mean AU $Co_{8hr}$ $C_{max}$, and $T_{max}$ between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-$\beta$) and treaeent difference (7) for AU $Co_{8hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.213-218
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• 1998

A novel in situ-gelling and mucoadhesive acetaminophen liquid suppository was developed to improve the patient compliance of conventional solid suppository. In this study, acetaminophen liquid suppository, Likipe $n_{R}$, ［aminophen/Poloxamer 407/Poloxamer 188/so4ium alginate (5/15/19/0.6%)] with relation temperature at 30-36 "C and suitable gel strength and bioadhesive force, dissolution pattern similar to conventional solid type suppository, Suspe $n_{R}$, was developed. Furthermore, the bioequivalence of two acetaminophen products was evaluated in 16 normal male volunteers (age 22-27 yr, body weight 56-72 kg) following sidle rectal administration. Test product was Likipe $n_{R}$ suppository (Dong-Wha Pharm. Corp., Korea)and reference product was Suspe $n_{R}$204-212 suppository (Hanmi Pharm. Corp., Korea). Both products contain 125 mg of acetaminophen. Four Suppositories of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of acetaminophen was accomplished using HPLC. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{-2}$4h/) (30.14$\pm$8.64 vs 27.98$\pm$ 6.53 $\mu$g .h/ml), maximum plasma concentration ( $C_{max}$) (3.29$\pm$0.87 vs 3.60$\pm$0.66 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.91 $\pm$0.55 vs 2.69$\pm$0.60 h). The differences of mean AUCo $_{24h}$, C-a. and T-between the two products (7.18%, 9.58% and 7.53%, respectively) were less than 20%. The power (1-7) and treatment difference ($\Delta$) for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ were more than 0.8 and less than 0.2, respectively at $\alpha$=0.1. The confidence limits for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ (-0.81 ~13.55%, -1.56~ 17.60 and -3.81 ~18.87%, respectively) were less than $\pm$ 20% at $\alpha$=0.1. These results suggest that the bioavailability of Likipe $n_{R}$ suppository is not significantly different from that of Suspe $n_{R}$ suppsitory. Therefore, two products are bio-equivalent based on the current results.results.lts.sults.results.lts.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.397-402
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• 2007

To evaluate the bioequivalence of two venlafaxine formulations, a standard 2-way randomized cross-over study was conducted in twenty-four healthy male Korean volunteers. A single oral dose of 75 mg of test formulation Venfaxine $OR^{(R)}$ (tablet) or reference formulation Efexor $XR^{(R)}$ (capsule) was administered with one-week washout period. Plasma concentrations of venlafaxine were assayed for over a period of 72 hours with a well validated method using liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). The $mean{\pm}S.D$. of maximum concentration $(C_{max})$ and elimination half-life $(t_{1/2})$ were $64.7{\pm}28.5$ ng/mL, $9.2{\pm}3.0$ h, and $67.2{\pm}30.2$ ng/mL, $9.9{\pm}3.5$ h for test and reference formulations, respectively. Time to reach maximum concentration $(T_{max})$ expressed in median value (range), for the test and the reference, were 10 h (6-14) and 8h (4-12), respectively. Similarly, area under the plasma concentration-time curve, from time zero to last sampling time $(AUC_t)$ and from time zero to time infinity $(AUC_{inf})$, for test and reference formulations were $1185{\pm}755$, $1326{\pm}896$ and $1124{\pm}737$, $1185{\pm}755$ $ng{\cdot}h/mL$, respectively. The parametric 90% confidence intervals on the mean of the differences between the two formulations (test-reference) of the log transformed values of $AUC_t$, and $C_{max}$ were 0.9630 to 1.1383 and 0.8650 to 1.0446, respectively. The overall results indicate that the two formulations are bioequivalent and can be prescribe interchangeably.

• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.41-49
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• 1993

The bioequivalence of two omeprazole enteric-coated products was evaluated in 16 normal male volunteers (age 26-32 yr, body weight 57-75 kg) following single oral administration. Test product was enteric-coated KD-182 tablet (Chong Kun Dang Corp., Korea) and reference product was $Rosec^{\circledR}$ capsule containing enteric-coated pellets of omeprazole (Yuhan Corp., Korea). Both products contain 20 mg of omeprazole. One tablet or capsule of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study ($2\;{\times}\;2$ Latin square method). Average drug concetrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products(p>0.05); the area under the concentrationtime curve to last sampling time (8 hr) $(AUC_{0-8hr})$ $(1946.5{\pm}675.3\;vs\;2018.3{\pm}761.6\;ng{\cdot}hr/ml)$, AUC from time zero to infinite $(AUC_{o-\infty})$ $(2288.6{\pm}1212.8\;vs\;2264.9{\pm}1001.3\;ng{\cdot}hr/ml)$, maximum plasma concentration $(C_{max})$ $(772.5{\pm}283.3\;vs\;925.8{\pm}187.7\;ng/ml)$, time to maximum plasma concentration $(T_{max})$ $(2.38{\pm}1.06\;vs\;2.34{\pm}1.09\;hr)$, apparent elimination rate constant $(k_{\ell})$ $(0.5339{\pm}0.2687\;vs\;0.5769 {\pm}0.2184\;hr^{-I})$, apparent absorption rate constant $(k_a)$ $(1.1536{\pm}0.5278\;vs\;0.9739{\pm}0.9507 hr^{-1})$ and mean residence time (MRT) $(3.13{\pm}0.73\;vs \;3.41{\pm}1.04\;hr)$. The differences of mean $(AUC_{0-8hr})$, $C_{max}$, $T_{max}$ and MRT between the two products (3.69, 19.83, 1.32 and 8.99%, respectively) were less than 20%. The power $(1-{\beta})$ and treatment difference $(\triangle)$ for $AUC_{o-8hr}$ $C_{max}$ and MRT were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different each other(p>0.05). These results suggest that the bioavailability of KD-182 tablet is not significantly different from that of $Rosec^{\circledR}$ capsule. Therefore, two products are bioequivalent based on the current results.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.219-224
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• 1998

The bioequivalence of two clarithromvcin products was evaluated with 16 normal male volunteers (age 23-28 yr, body weight 57.5-75.517g) following single oral dose. Test product was ReYon Clarithromycin tablets (ReYon Pharm. Corp., Korea) and reference product was Klarici $d_{R}$ tablets (Abbott Korea). Both products contain 250 mg of clarithromucin. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of clarithromycin was accomplished using a modified agar well diffusion bioassay. As a result of the assay validation, the quantification of clarithromycin in human serum by this technique was possible down to 0.03$\mu$g/ml using 100$\mu$l of serum. The coefficient of variation (C.V.) was less than 10%. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products P>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{24hr}$ (8.10$\pm$ 1.26 vs 8.22$\pm$ 1.627g . hr/ml), AUC from time zero to infinite (AU $Co_{\infty}$) (8.61 $\pm$ 1.28 vs 8.84$\pm$ 1.71 $\mu$g . hr/ml), maximum plasma concentration ( $C_{msx}$) (0.87$\pm$0.22 vs 0.88$\pm$0.19 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.69 $\pm$0.48 vs 2.56$\pm$ 0.51 hr). The differences of mean AU $Co_{24h}$, $C_{msx}$ and $T_{msx}$ between the two products (1.44, 1.39, and 4.65%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectivly. Although the power for $T_{max}$ was under 0.8, $T_{max}$. of the two products was not significantly different each other (p>0.05). These results suggest that the bioavailability of ReYon Clarithromycin tablets is not significantly different from that of Klarici $d_{R}$ tablets. Therefore, two products are bioequivalent based on the current results. results.sults.sults.s.s.s.s.s.s.s.