• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.21-26
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• 2005

A bioequivalence study of CKD $Cefaclor^{(R)}$ capsule (Chong Kun Dang Pharm Co., Ltd) to $Ceclor^{(R)}$ capsule (Lilly Korea 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 cefaclor dose of 250 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. An improved high-performance liquid chromatorgraphy (HPLC) analytical method with UV detection was used to determine plasma cefaclor concentration in human volunteers for 8 hr after oral drug administration. The area under the plasma concentration-time curve from time zero to 8 hr ($AUC_{0-8hr}$) was calculated by the linear trapezoidal rule. the $C_{max}$ (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 $AUC_{0-8hr}\;and\;C_{max}$. 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 $AUC_{0-8hr}$ ratio and the $C_{max}$ ratio for CKD $Cefaclor^{(R)}$ and $Ceclor^{(R)}$ were $0.9400{\leq}{\delta}{\leq}1.0345$ and $0.8858{\leq}{\delta}{\leq}1.1021$, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the of CKD $cefaclor^{(R)}$ capsule was bioequivalent to $Cefaclor^{(R)}$ capsule with respect to its bioavailability.

• Proceedings of the Korean Nutrition Society Conference
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• 2003.10a
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• pp.100-100
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• 2003

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.283-288
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• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.297-301
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• 1996

Plasma profile of niflumic acid following oral administration of talniflumate tablets (Somalgen) was compared to that of niflumic acid tablets in man. Plasma niflumic acid was assayed by HPLC method. Plasma niflumic acid profile from the tainiflumate tablets was similar to that from the niflumic acid tablets resulting in no differences in $AUC, C_max, t_max$ and MRT. It demonstrates that talniflumate is a prodrug of niflumic acid, and undergoes extensive first-pass biotransformation to niflumic acid. However, plasma niflumic acid concentration at 30 min after tainiflumate dosing was significantly (p<0.05) higher than that of niflumic acid dosing. The more potent analgesic activity of talniflumate than niflumic acid might be related to this higher plasma drug concentration at the earlier phase. Considering that tainiflumate is less irritant to gastrointestinal mucosa than niflumic acid, talniflumate seems to be advantageous over niflumic acid in terms of activity and side effects.

• Archives of Pharmacal Research
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• v.15 no.3
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• pp.246-250
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• 1992

Acetaminophen (AAP) and ranitidine (RT) were coadministered orally to nine rats, and the possible contribution of the gastric emptying to the plasma concentration profiles of them was examined. The drugs showed multiple plasma peaks similar to the respective ones after separated administration of each durg. IT Implies that there is no significant interaction between AAP and RT in terms of the gastric emptying or drug absorption. There were no significant linear correlations of the peak patterns (peak height and peak time) between AAP andd RT. It is contrary to the expectation from the biphasic gastric emptying (BGE) theory previously suggested for AAP and RT. The BGE theory. Therefore, seemed to have some draw-backs in explaining satisfactorily the multiple plasma peaks of AAP and RT. Two more doubts raised previously against the BGE theory were also discussed.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.247-252
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• 2000

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease. For the development of transdermal systems containing clenbuterol, two limiting factors - long lag time and low flux - must be overcome. In this study, we attempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of clenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Furthermore, the clenbuterol patch composed of 15% clenbuterol, 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levels in in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

• YAKHAK HOEJI
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• v.23 no.2
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• pp.111-118
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• 1979

It was previously reported that cytochrome P$_{450}$ content in liver was increased when Capsicum acetone extract was given chronically to rats. The present study is aimed to investigate the effect of capsaicin, a principal component of red pepper, on the drug metabolizing enzymes in rat liver. Capsaicin (5mg/kg) was given intraperitoneally once a day for seven days and zoxazolamine paralysis time and hexobarbital sleeping time were determined 24 hrs after the last dose of capsaicin. Plasma hexobarbital concentration was also determined five and 15 min after hexobarbital administration to rats. Zoxazolamine paralysis time and hexobarbital sleeping time were shortened by 31.6% and 37.1%, respectively, compared with control group. Plasma hexobarbital concentration was lowered by 26.2% after five min and by 35.2% after 15 min, respectively, compared with control group. However, administration of single dose of capsaicin did not affect the zoxazolamine paralysis time and hexobarbital sleeping time. Microsomal cytochrome P$_{450}$ content and NADPH-cytochrome C reductase activity were increased by 14.6% and 11.6%, respectively in the rats pretreated with capsaicin for seven days, while cytochrome b$_{5}$ content was not changed. These results suggest that treatment with capsaicin for seven days may induce the drug metabolizing enzyme in rat liver.

• Journal of the korean veterinary medical association
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• v.43 no.2
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• pp.169-175
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• 2007

최근 수의학에서도 여러 항생제에 내성이 있는 세균 감염이 확인되면서 기존에 사용되었던 항생제에 의한 치료 반응이 떨어지고 새로운 항생제가 도입되고 있다. 그러나 항생제 내성을 가진 세균의 출현을 방지하고 항생제에 의한 부작용을 최소화하기 위해 적절한 항생제 사용은 필수적이다. 세균 배양과 항생제 감수성 검사를 기본으로 항생제에 있어서의 약동학(pharmacodynamics)과 약역학(pharmacokinetics)을 바탕으로 항생제 치료에 대해 보다 정확히 접근할 수 있다. 세균에 대한 최소억제농도(minimum inhibitory concentration, MIC)와 최고혈장약물농도(peak plasma drug concentration, C max)를 비교하는 것은 항생제 선택의 기준이 된다.또한 MIC가 C max에 가까울수록 효과적인 치료를 위해서는 가능한 높은 용량을 사용해야 함을 의미한다.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.262-268
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• 2000

The bioequivalence of two tiropramide products was evaluated in 18 health male volunteers following oral administration. Test product was Tira $m^{R}$ tablet (Shin Poong SP-102) (Shin Poong Pharm. Co., Ltd.) and reference product was Tirop $a^{R}$ tablet (Dae Woong Pharm. Co., Ltd.) One capsule of the test and reference product containing 100 mg of tropramide.hydrochloride was administered to the volunteers by randomized two period cross-over study (2 $\times$ 2 Latin square method). The drug concentration in plasma was determined by GC/MS for over a period of 12hours after administration. Analysis of variance reveal that there are no differences in AUC (area under the plasma concentration-time curve from time zero to infinity), Cmax (maximum plasma concentration) and Tmax (time to reach Cmax). The differences of mean AUC, Cmax and Tmax between two products were 3.85, 1.47 and -3.6%, respectively. Minimum detectable differences (%) at $\alpha$=0.1 were all less than 20% given as a guideline (18.07, 17.00 and 20.69% for AUC, Cmax and Tmax, respectively). From these results, the two products are bioequivalent.ent.

• Journal of Pharmaceutical Investigation
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• v.24 no.4
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• pp.289-295
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• 1994

Pharmacokinetic drug interaction between phenytoin and verapamil was investigated following i.v. administration of two drugs concomitantly to rabbits. Verapamil was coadministered with phenytoin (5 mg/kg) to rabbits at the doses of 0.5,1 and 2 mg/kg, respectively. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 1mg and 2mg/kg of verapamil, respectively. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin should be administered with verapamil in clinical practice.