• Journal of Pharmaceutical Investigation
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• 제37권4호
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• pp.255-261
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• 2007

A bioequivalence study of $Nimegen^{TM}$ soft capsule (Medica Korea Pharma. Co., Ltd.) to $RoAccutane^{(R)}$ soft capsule (Roche Korea Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty healthy male Korean volunteers received each medicine at the isotretinoin dose of 60 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of isotretinoin were monitored by a high performance liquid chromatography (HPLC) for over a period of 48 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48 hr) was calculated by the linear trapezoidal rule method. $C_{MAX}$ (maximum plasma drug concentration) and $T_{MAX}$ (time to reach $C_{MAX}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t\;and\;C_{MAX}$. 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 $Nimegen^{TM}/RoAccutane^{(R)}$ were $log0.860{\sim}log0.98\;and\;log0.85{\sim}log1.00$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Nimegen^{TM}\;and\;RoAccutane^{(R)}$ with respect to the rate and extent of absorption.

• 한국안광학회지
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• 제12권2호
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• pp.67-78
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• 2007

시판중인 렌즈 보존액 중 가장 흔히 사용 또는 유통되고 있는 CLIWELL$^{TM}$에 대한 안점막자극성 시험을 식품의약품 안전청 고시에 따라 Draize법을 이용하여 그 자극성의 정도를 평가하고, 눈에 가해질 수 있는 잠재적인 독성을 평가하기 위하여, 배출물에 대한 도말표본 상에서 염증세포 및 비 염증성 유상피세포가 차지하는 비율과 함께 점안 14일 후 안구 중, 각막, 홍채, 망막 및 공막의 조직병리학적 관찰을 실시한 결과 다음과 같은 결과를 얻었다. 비 세척군에서는 점안 후 1, 2 및 3일에 국한하여, 각막과 결막에 경미한 자극이 관찰되어, 이 기간 동안의 평균 안점막 자극지수 MIOI가 각각 4.50, 1.67 및 0.67로 관찰되었으며, 세척군에서는 점안 후 1 및 2일에 국한하여, 결막에서 경미한 자극성이 인정되었고, 이때 MIOI는 각각 0.67로 관찰되었다. 따라서 CLIWELL$^{TM}$은 세척군 및 비 세척군 모두에서 MIOI가 모든 관찰 기간에서 4.50이하로 관찰되었으며, IAOI 역시 점안 1일 후 4.50으로 관찰되어 무자극성 물질로 판단되었다. 한편 배출물에 대한 염증성 세포의 비율은 무처치 대조군과 비교하여 점안 1일 후 유의성 있는 염증세포 비율의 증가가 비세척군에 국한하여 인정된 이외에 의미 있는 변화는 인정되지 않았다. 또한 안구의 조직병리학적 검사에서 각막, 홍채, 망막 및 공막 모두에서 무처치 대조군과 비교하여 의미 있는 변화는 인정되지 않았다.

• 한국안광학회지
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• 제11권4호
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• pp.299-310
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• 2006

시판중인 렌즈 보존액 중 가장 흔히 사용 또는 유통되고 있는 $SOLOCARE^{TM}$에 대한 안점막자극성시험을 식품의약품 안전청 고시에 따라 Draize법을 이용하여 그 자극성의 정도를 평가하고, 눈에 가해질 수 있는 잠재적인 독성을 평가하기 위하여, 배출물에 대한 도말표본 상에서 염증세포 및 비 염증성 유상피세포가 차지하는 비율과 함께 점안 후 안구 중, 각막, 홍채, 망막 및 공막의 조직병리학적 관찰을 실시한 결과 다음과 같은 결과를 얻었다. 비 세척군에서는 점안 후1, 2 및 3일에 국한하여, 각막과 결막에 경미한 자극이 관찰되어, 이 기간 동안의 평균 안점막 자극지수(Mean Index of Ocular Irritation; MIOI)가 각각 4.33, 3.33 및 2.00으로 관찰되었으며, 세척군에서는 점안 후 1 및 2일에 국한하여, 결막에서 경미한 자극성이 인정되었고, 이때 MIOI는 각각 3.00과1.33으로 관찰되었다. 따라서 $SOLOCARE^{TM}$는 세척군 및 비세척군 모두에서 MIOI가 모든 관찰기간에서 5.00 이하로 관찰되었으며, 관찰기간 중 MIOI의 최대값인 IAOI(The Index of Acute Ocular Irritation) 역시점안 1일후 4.33로 관찰되어 무자극성 물질로 관찰되었다. 한편 배출물에 대한 염증성 세포의 비율은 무처치 대조군과 비교하여 점안초기 유의성은 인정되지 않았으나, 다소 증가된 경향을 나타낸 이외 의미있는 변화는 인정되지 않았다. 또한 안구의 조직병리학적 검사에서 각막, 홍채, 망막 및 공막 모두에서 무처치 대조군과 비교하여 의미 있는 변화는 인정되지 않았다.

• Journal of Pharmaceutical Investigation
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• 제31권1호
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• pp.49-55
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• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, $Nicetile^{TM}$ (Dong-A pharmaceutical Co., Ltd.) and $Neurocetil^{TM}$ (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, $22.80{\pm}2.76$ year in age and $63.07{\pm}7.98\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the $Nicetile^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 94.87% and 87.17%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 15.58% and 19.16% $AUC_t\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-11.84{\sim}6.41$ and $-10.57{\sim}11.88$for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Neurocetil^{TM}$ tablet is bioequivalent to $Nicetile^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.125-131
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• 2010

A bioequivalence study of LANIDIEM$^{(R)}$ tablet 4 mg (Samil. Co., Ltd.) to Vaxar$^{(R)}$ tablet 4 mg (GlaxoSmithKline Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Forty healthy male Korean volunteers were enrolled in the study and thirty six volunteers completed the study according to the protocol. Thirty six volunteers received each medicine at the lacidipine dose of 4 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of lacidipine were monitored by a high performance liquid chromatography - tandem mass spectrometry (LC-MS/MS) for over a period of 24 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. 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 LANIDIEM$^{(R)}$/Vaxar$^{(R)}$ were log 0.8102~log 1.0417 and log 0.8493~log 1.1439, respectively. These values were within the acceptable bioequivalence intervals of log 0.80~log 1.25. Thus, our study demonstrated the bioequivalence of LANIDIEM$^{(R)}$ tablet 4 mg and Vaxar$^{(R)}$ tablet 4 mg with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.209-214
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• 2004

A bioequivalence study of $Roxithrin^{TM}$ tablet (Kukje Pharma. Ind. Co., Ltd.) to $Rulid^{TM}$ tablet (Han Dok Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the roxithromycin dose of 300 mg in a $2{\times}2$ crossover study. There was a one-week wash-out period between the doses. Plasma concentrations of roxithromycin were monitored by a high-performance liquid chromatography for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Roxithrin^{TM}/Rulid^{TM}$ were 1.00 - 1.13 and 0.98 - 1.10, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25. Thus, our study demonstrated the bioequivalence of $Roxithrin^{TM}$ and $Rulid^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.421-427
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• 2008

The purpose of the present study was to evaluate the bioequivalence of two etodolac capsules, Kuhnillodin capsule (Kuhnil. Co., Ltd., Seoul, Korea) as reference drug and Etodin capsule (Myungmun Pharm. Co., Ltd., Seoul, Korea) as test drug, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-three healthy male Korean volunteers received one capsule at the dose of 200 mg etodolac in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of etodolac were monitored by a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 24 hr after the administration. $AUC_{0-24\;hr}$ was calculated by the linear trapezoidal rule method. $C_{max}$ and $T_{max}$ were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed $AUC_{0-24\;hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-24\;hr}$ ratio and the $C_{max}$ ratio for Etodin/Kuhnillodin were $\log\;0.97{\sim}\log\;1.08$ and $\log\;0.89{\sim}\log\;1.19$, respectively. These values were within the acceptable bioequivalence intervals of $\log\;0.80{\sim}\log\;1.25$. Thus, our study demonstrated that Etodin was bioeqiovalent to Kuhnillodin preparation when the rate and extent of absorption between two preparations were compared.

• 한국임상약학회지
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• 제8권2호
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• 약학회지
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• 제55권4호
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• pp.324-331
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• 2011

Although the dissolution test can serve as an effective tool for quality control and predictor of in vivo performance, there are a number of drugs with no established dissolution specifications in Korean Pharmaceutical Codex (KPC). Among those commercially available, Piracetam Tablets and Fenoterol hydrobromide Tablets were selected to develop the dissolution testing method. The dissolution condition was determined based on the "Guidelines on Specifications of Dissolution tests for Oral dosage forms" of Korea Food & Drug Administration (KFDA). The dissolution test for Piracetam Tablets was carried out under sink condition with distilled water as dissolution medium, paddle rotation speed at 50 rpm and medium volume of 900 ml. More than 80% of its label claim was released within 30 min. In case of Fenoterol hydrobromide Tablets, distilled water was also found to be suitable to ensure sink condition. The rotation speed of 50 rpm and 900 ml of dissolution medium were used to evaluate the dissolution profile. The dissolution rate of fenoterol hydrobromide was over 90% in 15 min. The HPLC analysis methods were validated in terms of accuracy, precision, specificity, linearity, quantitation limit and range. The results suggested that the analytical methods used are simple and suitable to measure the dissolution rate of piracetam and fenoterol hydrobromide. Therefore, the analysis methods could be utilized in setting dissolution specifications of Piracetam Tablets and Fenoterol hydrobromide Tablets in the revised version of KPC.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.505-511
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• 2004

A bioequivalence study of $Bestidine^{TM}$ tablets (Choong Wae Pharma. Corp., Korea) to Dong-A $Gaster^{TM}$ (Dong-A Pharmaceutical Co., Ltd., Korea) tablets was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the famotidine dose of 40 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of famotidine were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. 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 Cmax ratio for $Bestidine^{TM}/Gaster^{TM}$ were log 0.90-log 1.06 and log 0.98-log 1.20, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Bestidine^{TM}$ and $Gaster^{TM}$ with respect to the rate and extent of absorption.