• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2007년도 추계학술대회
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• pp.86-86
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• 2007

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• 한국임상약학회지
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• 제15권1호
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• pp.55-60
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• 2005

The aim of this study is to investigate the effect of naringin on the pharmacokinetics of tamoxifen in rats. Tamoxifen (10 mg/kg) was administered orally 0.5 h and 3 days after oral administration of naringin (5 mg/kg). The plasma concentrations of tamoxifen were increased significantly tv naringin compared to control. Absorption rate constant ($K_a$) of tamoxifen with naringin was increased significantly compared to that of the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations ($C_{max}$) of tamoxifen with naringin were significantly higher than those of the control. Consequently, the relative bioavailability (R.B${\%}$) of tamoxifen with naringin was 2-3-fold higher than the control, and absolute bioavailability (A.B${\%}$) of tamoxifen were significantly higher (p<0.05 with coadministration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with naringin might be associated with the inhibition by naringin of an efflux pump P-glycoprotein and the first-pass metabolizing enzyme CYP3A4.

• 한국임상약학회지
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• 제15권1호
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• pp.50-54
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• 2005

The purpose of this study is to investigate the effect of aspirin on the pharmacokinetics of pranoprofen by oral coadministration of pranoprofen (5 mg/kg) with aspirin (5, 10 and 20 mg/kg) in Sprague-Dawley rats. After oral coadministration of pranoprofen with aspirin, the area under the plasma concentration-time curves (AUC) of pranoprofen was increased significantly by 10 mg/kg (p<0.05) and 20 mg/kg (p<0.01) of aspirin coadministration, and peak concentrations ($C_{max}$) of pranoprofen was increased significantly by coadministration of 20 mg/kg aspirin (p<0.05) compared to pranoprofen alone. Relative bioavailabilities (RB${\%}$) of pranoprofen in coadmistration were higher (from 1.42 to 1.67 fold) than control. The half-lives ($t_{1/2}$) of pranoprofen in coadministration were increased significantly (p<0.05) by 20-mg/kg aspirin. Based on these results, we might be considered that the pharmacokinetics of pranoprofen would be affected by coadministration of aspirin, by inhibit its metabolism in the liver and the tubular secretion of the kidney with the same acidic property. It should take into consideration in dosage regimen of pranoprofen when coadministration of pranoprofen with aspirin in treatment of rheumatoid arthritis.

• Journal of Ginseng Research
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• 제46권2호
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• pp.206-213
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• 2022

Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.

• 약학회지
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• 제57권6호
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• pp.412-419
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• 2013

Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

• 약학회지
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• 제35권5호
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• pp.379-383
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• 1991

This study was attempted to investgate the pharmacokinetics of theophylline (4 mg/kg i.v) in the rabbits pretreated with propranolol (1 and 2.5 mg/kg/hr, infusion) for four hours. The plasma concentration and AUC of theophylline were increased in rabbits pretreated with propranolol as compared with those of normal rabbits. The amount of cumulative urinary excretion and renal clearance and total body clearance were decreased in rabbits pretreated with propranolol as compared with those of normal rabbits. The apparent volume of distribution was slightly affected by change of the clearance of theophylline. From the results of this experiment, it is desirable that dosage regimen of theophylline should be adjusted when theophylline combined with propranolol in clinical pharmacy practice.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 1996년도 정기총회 및 추계학술대회
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• pp.36-36
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• 1996

• 한국임상약학회지
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• 제21권2호
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• pp.74-80
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• 2011

Population pharmacokinetics for gentamicin were compared with 20 Korean patients (14 male and 6 female) and 25 Caucasian appendicitis patients (16 male and 9 female). Two to six blood specimens were collected from all patients at the following times : just before a regularly scheduled infusion and at 0.5 hour after the end of a 0.5 hour infusion. Nonparametric expected maximum(NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant(K), the slope(KS) of the relationship between K versus creatinine clearance(Ccr), the apparent volume of distribution (V), the slope(VS) of the relationship between V versus weight, gentamicin clearance(CL) and the slope(CS) of the relationship between CL versus Ccr and the V. The output includes two marginal probability density function(PDF), means, medians, modes, variance, skewness, kurtosis, and CV%. The mean K(KS) were$0.402{\pm}0.129hr^{-1}$ ($0.00486{\pm}0.00197[hr{\cdot}mL/min/1.73m^2]^{-1}$) and $0.425{\pm}0.137hr^{-1}$($0.00432{\pm}0.00168[hr{\cdot}mL/min/1.73m^2]^{-1}$) for Korean and Caucasian populations, respectively. The mean V(VS) were not different at $14.3{\pm}3.69L$($0.241{\pm}0.0511L/kg$) and $15.8{\pm}4.81L$($0.236{\pm}0.0531L/kg$) for Korean and Caucasian populations, respectively (P>0.2). The mean CL(CS) were $5.68{\pm}1.69L/hr$ ($0.0714{\pm}0.0222L/kg[hr{\cdot}mL/min/1.73m^2]$) and $6.29{\pm}1.84L/hr$ ($0.0629{\pm}0.0189L/kg[hr{\cdot}mL/min/1.73m^2]$) for Korean and Caucasian populations, respectively. There are no differences in gentamicin pharmacokinetics between Korean and Caucasian appendicitis patients.

• Journal of Pharmaceutical Investigation
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• 제39권2호
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• pp.111-115
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• 2009

The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.

• 한국임상약학회지
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• 제22권1호
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• pp.1-8
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• 2012

항혈소판제인 티크로피딘과 항고혈압제인 니칼디핀과의 약동학적 상호작용 연구를 위하여 티크로피딘 (3 또는 10 mg/kg)과 니칼디핀의 경구 (4 mg/kg) 및 정맥 (12 mg/kg) 투여하여 본 연구를 시행하였다. 연구방법: 티크로피딘이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 결 과: 티크로피딘과 니칼디핀의 병용투여 시 티크로피딘이 니칼디핀의 약물동태 파라미터에 미치는 결과는 다음과 같다. 티크로피딘은 CYP3A4 효소의 활성을 저해 하였으나 P-gp활성에는 영향을 미치지 못하였다. 니칼디핀의 혈중농도곡선하면적 (AUC)는 대조군에 비해 티크로피딘 10 mg/kg 병용투여군에서 유의성 (p < 0.05)있게 증가되었다. 상대적 생체이용률 (RB)은 티크로피딘 병용투여군에서 115-143%로 증가하였다. 결 론: 본 논문에서 흰쥐에 티크로피딘과 니칼디핀을 병용경구투여 시 니칼디핀의 생체이용률 (bioavailability)이 유의성 (p < 0.05)있게 증가된 것은 티크로피딘이 대사효소인 CYP3A4를 억제하여 소장과 간장에서 초회통과효과 (first-pass metabolism)를 감소 시켰기 때문인 것으로 사료된다. 본 실험결과를 토대로 인체에서 티크로피딘과 니칼디핀의 상호작용을 검토한 후 투여용량을 조절하는 것이 바람직하다고 사료된다.