• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.296-302
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• 1998

The bioequivalence of two cyclosporin A products was evaluated in 26 normal male volunteers (age 25 ~33 yr, body weight 56~84 kg) following single oral administration. Test product was a hard capsule containing the granule of cyclosporin A (Chong Kun Dang Corp., Korea) and reference product, Sandimmun", was a soft capsule containing surfactant, oil, alcohol and cyclosporin A (Sandoz, Swiss). Both products contain 100 mg of cyclosporin A. Four capsules 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). Average drug concentrations at each sampling time and pharmacokinetic parameters were not significantly different between two products (p>0.05); the area under the concentration-time curve to last sampling time (24 hr) (AU $Co_{24}$) (5034.8$\pm$ 1760.6 vs 4635.4$\pm$ 1158.9 ng . h/ml), maximum plasma concentration ( $C_{max}$) (1002.7$\pm$353.1 vs 980. 4$\pm$ 171.7 ng/71), and mean residence time (MRT) (6.16$\pm$0.81 vs 5.64$\pm$0.50 h). The differences of mean AUC 7-,4,7~, T_ and MRT between the two products (7.93,2.22,16 and 8.39%, respectively) were less than 20% given as a guideline. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24}$, $C_{max}$ and MRT were more than 0.8 and less than 0.2, respectively. Although $T_{max}$ of the two products was significantly different each other (p<0.05), $T_{max}$ might be an insignificant parameter because cyclosporin A generally requires long-term administration. From these results, the two products are bioequivalent.alent.t.

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.323-330
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• 1995

Ceftezole pivaloyloxymethyl ester(CFZ-PV) was synthesized to improve oral absorption and bioavailability of parent drug by esterification of ceftezole(CFZ) with chloromethyl pivalate. The successful synthesis of CFZ-PV was conformed by spectroscopic analysis. Partition coefficient studies showed that CFZ-PV is more lipophillic than CFZ. The pharmacokinetic characteristics of CFZ-PV and CFZ were compared following oral administrations of these compounds to rabbits. The amount of CFZ in plasma was determined with an HPLC method. The ester compound (prodrug) was not detected in plasma following oral administration of CFZ-PV, and although CFZ-PV had not microbiological activity in vitro, the plasma taken after oral administration of CFZ-PV had microbiological activity. From above observations, it was noted that CFZ-PV is rapidly hydrolyzed to CFZ in the body. And the oral absorption of CFZ-PV was increased by yielding 2-fold bioavailability rather than CFZ. Therefore, CFZ-PV could be a novel prodrug of CFZ which can improve the oral bioavailability of CFZ.

• YAKHAK HOEJI
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• v.45 no.5
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• pp.506-512
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• 2001

Ketoprofen (KP) was formulated as a transdermal patch using the percutaneous penetration enhancers sorbitan monmmleate(SMO), polyvinylpyrrolidone(PVP). The control patch without penetration enhancers showed a KP flux of 8.9$\pm$0.75$\mu\textrm{g}$/$\textrm{cm}^2$/h The flux was increased in proportion to the concentration of SMO added. Furthermore, lag times were decreased upon addition of SMO. Conversely; the skin flux of KP was decreased in proportion to the concentration of PVP added. Pharmacokinetic parameters including $C_{max}$, $T_{max}$, and AUC were increased when SMO was added. However, $C_{mas}$ significantly decreased by the addition of PVP. $T_{max}$ was not significantly different in 2%, 4%, and 8% PVP patches. Patches containing 4% PVP showed the highest AUC value (19.158$\mu\textrm{g}$.h/ml). We found that the effectiveness of the two percutaneous penetration enhancers for topical KP patches was similar, with the addition of appropriate amounts of HPC modifying both skin flux and lag time of KP in the patches. In conclusion, it is possible to manufacture KP patches exhibiting high AUC, high skin flux, and short lag time using percutaneous penetration enhancers of SMO and PVP.

• Journal of Pharmaceutical Investigation
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• v.14 no.1
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• pp.11-18
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• 1984

This paper was attempted to study on the effect of metoclopramide or propantheline on the absorption rate and bioavailability and pharmacokinetic parameter of fluorouracil in rats and rabbits. The result are as follows; Metoclopramide increased the absorption rate of fluorouracil but propantheline decreased in situ experiment with rat small intestine. Metoclopramide increased the blood level and relative bioavailability and absorption rate constant of fluorouracil in rabbits. Prolonged the peak blood level (tmax) and decreased the absorption rate constant (Ka) but did not affect the blood level and relative bioavailability of fluorouracil in rabbits. As a matter of fact, it is considerd that the coadministration of metoclopramide or propantheline is more desirable than the single administration of fluorouracil for available dosage regimen.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.97-106
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• 2012

The pharmacokinetics/pharmacodynamics analysis software NONMEM$^{(R)}$ output provides model parameter estimates and associated standard errors. However, the standard error of empirical Bayes estimates of inter-subject variability is not available. A simple and direct method for estimating standard error of the empirical Bayes estimates of inter-subject variability using the NONMEM$^{(R)}$ VI internal matrix POSTV is developed and applied to several pharmacokinetic models using intensively or sparsely sampled data for demonstration and to evaluate performance. The computed standard error is in general similar to the results from other post-processing methods and the degree of difference, if any, depends on the employed estimation options.

• Korean Journal of Clinical Pharmacy
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• v.6 no.2
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• pp.14-18
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• 1996

This study was attempted to investigate the dissolution rate and the bioavailability after oral administration of commercially available norfloxacin tablets in rabbits. The dissolution test was conducted in artificial gastric juice using basket method with for norfloxacin preparations (A, B, C and D) which were chemically equivalent. The results were as follows ; The dissolution rate was increased in the order of four different brand A>D>B>C. Area under the plasma concentration curve and peak plasma concentration were increased in the order of brand A>D>B>C. Absorption rate constant and peak time were increased in the order of brand B>A>C>D, and there was a little difference in elimination rate constant and biological half-life. The correlation of the dissolution rate and relative bioavailability showed significant linear relationship. From the results of this experiment, the bioavailability of norfloxacin tablets in rabbits may be predicted from the results of dissolution rate studies.

• Korean Journal of Clinical Pharmacy
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• v.10 no.1
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• pp.19-24
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• 2000

The effect of cimetidine on the pbarmacokinetic parameters of cyclosporine (intravenous administration) were determined in 6 healthy volunteers (22-48 years old, 48-62 kg) by cross-over design. Cyclosporine and cyclosporine metabolites in whole blood were analysed by fluororescence polarization immunoassay (TDx-FLX). The blood concentrations of cyclosporine After pretreatment with cimetidine (200 mg bid, for 3days) were increased significantly at 8-12 hrs compared to the control (p<0.05). The ratios of blood concentrations of cyclosporine metabolites (M1, M17) to parent drug were decreased significantly at 8-12 hrs (p<0.05). Total body clearance (CL) was also decreased significantly (p<0.05), and area under the curve $(AUC,\%)$ was increased but not significant.

• YAKHAK HOEJI
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• v.27 no.2
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• pp.149-154
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• 1983

The effect of hydrochlorothiazide on the pharmacokinetics of carteolol in rabbits was studied. Animals were divided into two groups (group I and group II). Group I received carteolol (12mg/kg) and group II received carteolol (12mg/kg) with hydrochlorothiazide (20mg/kg) orally. The carteolol concentration in serum was measured by spectrofluorometric method and its pharmacokinetic parameter values were calculated. The serum concentration of carteolol in group II was significantly increased when compared with those in group I at 10min (p<0.01), and at 30min (p<0.05) after p. o. administration. In addition, the absorption rate constant of carteolol in group II was slightly increased and Tmax of carteolol in group II was significantly shortened (p<0.05) and Cmax of carteolol in group II was significantly increased (p<0.02) when compared with those in group I. But elimination rate constant and biological half-life of carteolol were similar in both groups.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.243-243
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• 1996

백금착물 항암제 후보물질로서 합성된 KBP31705-Cl27, KBP30603-901을 기존 화합물인 cisplatin 및 carboplatin과 pharmacokinetic profile을 비교 검토하였다. 웅성 Sprague-Dawley rat을 sodium pentobarbital 마취하에서 방광 및 대퇴동맥과 정맥에 polyethylene tubing을 사용하여 catheterization시켰다. Urine 배출이 안정화되었을 때 대퇴정맥내로 cisplatin과 KBP31705-Cl27은 2 mg/kg, carboplatin과 KBP 30603-901은 20mg/kg 용량으로 주사한 후 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120 분에 대퇴동맥으로부터 혈액을 채취하였으며 urine은 약물투여 후 1시간 간격으로 4시간동안 채취하였다. Plasma와 urine중의 platinum농도는 inductively coupled plasma-mass spectrometer를 사용하여 측정하였고, pharmacokinetic parameters는 non-linear least square computer Program인 PCNONLIN을 이용하여 산출되었다. 혈중 platinum농도와 시간의 관계에서 KBP31705-Cl27은 cisplatin과 비교하여 alpha-phase에서 혈중 농도는 낮지만 비슷한 양상을 나타내었고, beta-phase에서는 비교적 느리게 소실됨을 보였다. Urine으로 4시간동안 배출된 platinum양은 각각 투여량의 52, 56%로서 두 약물에서 비슷하였다. 또한 KBP30603-901은 carboplatin과 비교하여 alpha-phase는 거의 비슷한 패턴을 나타내었으나, beta-phase는 훨씬 느리게 감소하여 반감기가 길다는 것을 보여 주었으며 또한 이것은 urine으로 4시간동안 배출된 platinum양이 KBP30603-901의 경우 투여량의 46%로서 carboplatin의 59%보다 적게 배출된다는 data와도 일관됨을 보여주었다. 이상의 결과로 볼 때 KBP30603-901이 다른 백금착물 항암제보다 체내에 머무르는 시간이 길어 혈중에서 보다 오랜 시간동안 머물러 높은 유효농도를 유지할 수 있을 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• v.19 no.2
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• pp.93-98
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• 1989

The study was performed to compare the dissolution, diffusion and absorption characteristics using Sartorius dissolution and absorption simulator and in vivo bioavailability of commercially available rifampicin capsules. Both brands C and F showed similar dissolution patterns and absorption properties through artificial gastric barrier in Sartorius simulator. Diffusion rate constants through the membrane of brands C and F were $3.04\;{\times}40^{-3}$ and $2.88\;{\times}\;10^{-3}cm/min$, respectively. Rifampicin capsules were administered orally to six fasted healthy volunteers according to cross-over design. The pharmacokinetic parameters between brands C and F, maximum plasma drug concentration$(C_{max})$, the time to reach $C_{max}$, absorption rate constant and area under the curve $(AUC_{0-24hr})$, elimination rate constant, and amount of drug excreted in urine were 6.11 and $7.27\;{\mu}g/ml$, 2.71 and 1.52 hr, 0.6371 and $1.6456 hr^{-1}$, 57.84 and $57.28\;{\mu}g\;{\cdot}\;hr/ml$, 0.1891 and $0.1734 hr^{-l}$, 119.98 and 119.93 mg, respectively. On the basis of experimental results, it was concluded that the bioavailability of brand C rifampicin capsules was almost the same as that of brand F rifampicin capsules.