• Biomolecules & Therapeutics
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• 제6권2호
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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.

• Biomolecules & Therapeutics
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• 제6권2호
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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.

• 대한수의학회지
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• 제35권4호
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• pp.815-822
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• 1995

The toxicokinetics of rifapentine was studied after an oral administration to beagle dogs. High-performance liquid chromatography(HPLC) using column-switching technique was performed to determine the serum concentrations of rifapentine. The pharmacokinetic profiles of rifapentine were analysed using one-compartment open model. Following a single oral administration of 10mg/kg, pharmacokinetic parameters were determined as follows: maximum serum concentration($C_{max}$), $28.90{\mu}g/ml$; maximum concentration time($T_{max}$), 3.7hr; elimination half-life($t_{1/2}$, 4.7hr; area under the curve(AUC), $339.0{\mu}g{\cdot}hr/ml$; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant($k_a$), $0.445hr^{-1}$; elimination rate constant($k_{el}$), $0.148hr^{-1}$. After 6 month multiple oral doses of 10mg/kg/day, parameters were as follows: $C_{max}$, $34.40{\mu}g/ml$; $T_{max}$, 2.6hr; $t_{1/2}$, 6.7hr; AUC, $391.3{\mu}g{\cdot}hr/ml$; Vd/F, 0.291/kg; $k_a$, $0.976hr^{-1}$; $k_{el}$, $0.104hr^{-1}$. The consistant kinetic parameters after a single and multiple oral administration show that there was no accumulation of rifapentine after 6 month oral administration. We also simulated the concentration of rifapentine after oral multiple administration of 10 and 50mg/kg/ day, based on the parameters obtained form the single administration. The measured serum concentrations of rifapentine were well fitted to the simulated results. The simulated results show that rifapentine readily reaches to steady-state after about 3 doses and the steady-state serum concentrations($C_{ss}$) are fluctuated in between $2.2{\sim}25.2{\mu}g/ml$, and $10.6{\sim}125.2{\mu}g/ml$ at the doses of 10 and 50mg/kg/day, respectively.

• 한국어병학회지
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• 제23권3호
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• pp.357-367
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• 2010

아목시실린(Amoxicillin trihydrate; Amox)을 뱀장어(평균 체중 $220{\pm}10\;g$)에 1일 1회 경구투여(40 및 80 mg/kg body weight) 및 정맥투여(1 mg/kg)한 다음, 경시적(0시간~720시간)으로 혈장내 Amox의 잔류농도를 분석하였다. 40 및 80 mg/kg 농도로 경구투여한 모든 시험구에서 투여 6시간째 각각 $3.3{\pm}0.5$ 및 $3.4{\pm}0.1\;{\mu}g/ml$로 최대혈중농도를 나타내었다. Amox의 모든 시험구는 투여 720시간째 혈중에서 검출되지 않았다. Amox의 경구투여방법에 따른 뱀장어 체내 약물 혈중농도 측정결과를 바탕으로 WinNonlin program을 이용한 2-compartment model로 하여 Amox의 흡수, 배설, 반감기 등 약물동태학적 매개변수(parameter)를 조사하였다. 2-compartment model을 이용한 분석을 통하여 40 및 80 mg/kg Amox를 경구투여한 경우, 혈장농도-시간곡선하 면적(AUC)은 각각 464 및 $667\;{\mu}g{\cdot}h/ml$, 혈중최고농도의 도달시간(Tmax)은 2.1 및 3.6 hr, 혈중최고농도(Cmax)는 3.04 및 $3.4\;{\mu}l/ml$로 계산되었다. 1 mg/kg Amox을 정맥 투여한 경우, 혈장농도-시간곡선하 면적(AUC)은 $748\;{\mu}g{\cdot}h/ml$, 혈중최고농도(Cmax)는 $4.2\;{\mu}l/ml$로 계산되었다. 1일 1회 단독으로 40 및 80 mg/kg Amox를 각각 경구 투여시의 뱀장어내 생체내이용율(F%; bioavailability)은 각각 1.6, 1.1%로 매우 낮게 나타났다. 이러한 결과는 아목시실린을 삼수화물 형태로 사용함에도 낮은 어류내 생체내이용율을 가진다는 사실을 알 수 있다.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.59-65
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• 2006

The purpose of this study was to evaluate the bioequivalence of two amlodipine maleate tablets, SKAD tablet (SK Pharma. Co., Ltd., Seoul, Korea, reference drug) and A-PINE tablet (Daewon Pharm. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male volunteers, $22.79\;{\pm}\;1.86$ years in age and $70.08\;{\pm}\;8.68$ kg in body weight, were divided into two groups and a randomized $2\;{\time}\;2$ crossover study was employed. After a tablet containing 6.42 mg of amlodipine maleate was orally administrated, blood was taken at predetermined time intervals over a period of 144 hr and concentrations of amlodipine in plasma were monitored using LC-MS/MS. Pharmacokinetic parameters such as $AUC_t$ (the area under the plasma concentration-time curve from time zero to 144 hr), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were calculated and analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$ and $C_{max}$, and untransformed $T_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for A-PINE/SKAD were $log\;0.9429{\sim}log \;1.1476$ and $log\;0.9l46{\sim}log\;1.1488$, respectively. Since these values were within the acceptable bioequivalence intervals of $log\;0.80{\sim}log\;1.25$, recommended by KFDA, it was concluded that A-PINE tablet was bioequivalent to SKAD tablet, in terms of both rate and extent of absorption.

• 한국식품영양학회지
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• 제21권4호
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• pp.397-402
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• 2008

Over the past few years, anthocyanin has been demonstrated to exert potentially anti-oxidative and bioavailability effects including anti-cardiovascular disease and cancer-preventive effects in humans. This study was conducted to assess the toxicity of anthocyanin extracts from black soybean seed coats via oral administration in a mice feeding test. The final anthocyanin-containing products induced signs of toxicity on mortality in the 4-week feeding test. The incidence of clinical signs and changes in body and organ weight were also not observed in all anthocyanin-treated groups as compared with the control groups. In hematology analysis, RBC indices concluding MCV, MCH, and MCHC and WBC differential counting such a NEU, LYM, MONO, EOS, and BASO evidenced no significant differences between the anthocyanin treatment and control groups. The biochemical parameters in serum analysis - ALT, AST, BUN, Crea etc.- were also not significantly altered in those groups. Absolute and relative organ weights were not increased after 4 weeks of treatment with anthocyanin extracts in mice. In conclusion, anthocyanin extracts from the black soybean has biological activity without any toxic effects, which also suggests that the consumption of soy containing anthocyanin products may be a good source for health and medical supplies.

• 한국임상약학회지
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• 제18권2호
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• pp.106-113
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• 2008

The aim of this study was to evaluate the bioequivalence of two domperidone preparations. Bioequivalence assessment was conducted on 34 healthy volunteers who received two tablets (Domperidone Maleate, 12.72 mg/tablet) in the fasting state, in a randomized balanced $2{\times}2$ cross-over study design. This whole study was performed according to the implementation guidelines of the Korea Food Drug Administration. After dosing of two tablets, blood samples were collected serially for a period of 36 hours. Plasma was analyzed for domperidone by using LC/MS/MS assay method. The analysis system was validated in specificity, accuracy, precision, and linearity. $AUC_t$, (the area under the plasma concentration-time curve from the zero-time to 36 hr) was calculated through the trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma domperidone concentration-time data of each volunteer. No significant sequence effect was found for the bioavailability parameters indicating that the cross-over design was properly performed. The 90%-Confidence intervals of the $AUC_t$ ratio and the $C_{max}$ were from log 0.8007 to log 1.1240 and log 0.8645- log 1.2483, respectively. These values were within the acceptable bioequivalence intervals between 0.80 and 1.25. Therefore, this study demonstrated that two formulations have bioequivalence with respect to the rate and extent of absorption.

• 한국임상약학회지
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• 제7권2호
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• pp.51-63
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• 1997

The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.

• Asian-Australasian Journal of Animal Sciences
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• 제24권7호
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• pp.940-945
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• 2011

In order to determine whether oxalate from grasses affects feed intake, blood calcium (Ca) and other blood parameters of adult sheep, two feeding trials were conducted. In Trial 1, one group of sheep received guineagrass (0.47% soluble oxalate) and another group received setaria (1.34% soluble oxalate) for 28 d. In Trial 2, one group of sheep received guineagrass while another group received the same grass treated with an oxalic acid solution (at a rate of 30 g oxalic acid/kg dry matter of hay) for 72 d. All sheep received concentrate mixtures (0.5% of body weight) throughout the experiment. In both trials, it was observed that plasma Ca concentration (11.0-11.7 mg/dl) was significantly (p<0.05) lower in sheep fed high oxalate-containing grasses than in sheep fed low oxalate-containing grasses (12.4-13.7 mg/dl). No differences (p>0.05) were observed in concentrations of magnesium, phosphorus and parathyroid hormone in plasma between the feeding of low and high oxalate-containing grasses. In addition, no differences (p>0.05) were observed in roughage dry mater (DM) intake, total DM intake or body weight of sheep. This study suggests that sheep may consume oxalate-rich forage, but Ca bioavailability may decrease with increasing oxalate levels in the ration.

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.51-53
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• 2003

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, $Tenormin^{\circledR}$ Tablets in 20 healthy Korean volunteers. The volunteers received a single 50 mg dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration $(C_{max})$, time to reach peak plasma concentration $(T_{max})$, and terminal first order elimination half-life $(t_{1/2})$. No statistically significant difference was obtained between the $T_{max}$ values, and the logarithmic transformed AUC and $C_{max}$ values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and $C_{max}$ values of Sinil Atenolol Tablets over those of $Tenormin^{\circledR}$ Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of $T_{max}$ in $Tenormin^{\circledR}$ Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of $t_{1/2}$ between the two products were found comparable, and the mean $t_{1/2}$ values of $Tenormin^{\circledR}$ Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to $Tenormin^{\circledR}$ Tablets in both the rate and extent of absorption, indicating that Sinil Atenolol Tablets were bioequivalent to the reference product, $Tenormin^{\circledR}$ Tablets