신장장해 가토에서 Theophylline의 약물동태

차중권,이진환,최준식,김가나,범진필 조선대학교 약학연구소 1992 藥學硏究誌 Vol.14 No.1

This study was attempted to investigate the pharmacokinetics of theophylline in rabbits with folate induced renal failure. Plasma concentration and AUC of theopylline were increased in rabbits with folate induced renal failure compared with those of normal rabbits. Renal clearance and total body clearance were decreased in rabbits with folate induced renal failure compared with those of normal rabbits. Correlation of serum creatinine concentration and AUC, and correlation of serum creatinine clearance and renal clearance have linear relationship respectively. From the results of this experiment, it is desirable that dosage regimen of theophylline should be adjusted for effective and safe therapy in patient with renal failure in clinical pharmacy practice.

위장간 수술환자에서 겐타마이신의 임상약물동태

최준식,문홍섭,최인,범진필 朝鮮大學校 1997 藥學硏究誌 Vol.18 No.2

The purpose of this investigation was to determine pharmacokinetic parameter of gentamicin using nonlinear least square regression(NLSR) and Bayesian analysis in Korea normal volunteers and gastrointestinal surgical patients. Nonparametric expected maximum(NPEM) method for population pharmacokinetic parameters was used. Gentamicin was administered every 8 hours for 3 days by infusion over 30 minutes. The volume of distribution(V) and elimination rate constant(K) of gentamicin were 0.226±0.032, 0.231±0.063 L/㎏ and 0.357± 0.024, 0.337±0.041 hr^-1 for normal volunteers and gastrointestinal surgical patients using NLSR analysis. Population pharmacokinetic parameters. KS and VS were 0.00344±0.00049(hr·mL/min/1.73㎡)^-1 and 0.214±0.0502 L/㎏ for gastronintestinal surgical patients using NPEM method. The V and K were 0.216±0.048 L/㎏ and 0.336±0.043 hr^-1 for gastrointestinal surgical patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetic between NLSR and Bayesian analysis in gastrointestinal surgical patient.

The Influence of Assay Error Weight on Gentamicin Pharmacokinetics Using the Bayesian and Nonlinear Least Square Regression Analysis in Appendicitis Patients

Jin, Pil-Burm The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.5

The purpose of this study was to determine the influence of weight with gentamicin assay error on the Bayesian and nonlinear least squares regression analysis in 12 Korean appen dicitis patients. Gentamicin was administered intravenously over 0.5 h every 8 h. Three specimens were collected at 48 h after the first dose from all patients at the following times, just before regularly scheduled infusion, at 0.5 h and 2 h after the end of 0.5 h infusion. Serum gentamicin levels were analyzed by fluorescence polarization immunoassay technique with TDxFLx. The standard deviation (SD) of the assay over its working range had been determined at the serum gentamicin concentrations of 0, 2, 4, 8, 12, and 16 ${\mu}g$/mL in quadruplicate. The polynominal equation of gentamicin assay error was found to be SD (${\mu}g$/mL) = 0.0246-(0.0495C)+ (0.00203C$^2$). There were differences in the influence of weight with gentamicin assay error on pharmacokinetic parameters of gentamicin using the nonlinear least squares regression analysis but there were no differences on the Bayesian analysis. This polynominal equation can be used to improve the precision of fitting of pharmacokinetic models to optimize the process of model simulation both for population and for individualized pharmacokinetic models. The result would be improved dosage regimens and better, safer care of patients receiving gentamicin.

Stability of Paclitaxel with cephalosporines in 0.9% Sodium Chloride Injection and 5% Dextrose Injection During Simulated Y-site Administration : Y-Site 동시투여 동안 0.9% 생리식염수와 5% 포도당 용액에서의 Paclitaxel과 Cephalosporines의 안정성 연구

Jin Pil Burm 한국임상약학회 2003 한국임상약학회지 Vol.13 No.2

Paclitaxel과 cephalosporines(제 1세대인 ceftezole sodium과 cephradine, 제2세대인 cefamandole sodium과 cefmetazole sodium, 제3세대인 cefoperazone sodium과 cefotaxime sodium 그러고 제4세대인 cefepime hydrochloride)을 포도당주사액 그리고 염화나트륨주사액과 함께 Y-Site 장치를 써서 환자에게 주입할 때 paclitaxel의 안정성에 관하여 연구하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml과 cephalosporines 20 mg/m을 각각 1 : 1로 혼합한 후 0, 1, 2, 4, 12시간 시점에서 paclitaxel의 농도를 HPLC로 분석하였다. 방해물질에 의한 분석오차를 줄이기 위해 분석법을 여러 상태에서 확인하였으며, 각 농도에서 3차례씩 실험하였고 각 샘플은 2차례 반복하여 HPLC로 분석하였다. 분석전에 각 시료의 투명도, 색의 변화, 침전상태 및 pH를 검사하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml와 cephalosporines 20 mg/ml를 각각 혼합하였을 때 12시간 동안 안정하였으며, 주사액의 혼탁이나 색의 변화 및 침전은 나타나지 않았으며 pH도 변하지 않았다.

Effects of Amlodipine on the Pharmacokinetics of Warfarin after Oral and Intravenous Administration of Warfarin in Rats

( Jin Pil Burm ),( Dong Hyun Choi ),( Yong Ji Piao ),( Eun Joo Choi ),( Jun Shik Choi ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.4

The aim of this study was to investigate the effect of amlodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of amlodipine (0.1 or 0.4 mg/kg) in rats. The effect of amlodipine on the P-glycoprotein (P-gp) as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Amlodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration (IC50) of 9.1 μM. Compared to those animals in the oral control group (warfarin without amlodipine), the area under the plasma concentration-time curve (AUC) of warfarin was signifi cantly greater (0.1 mg/kg, p<0.05; 0.4 mg/kg, p<0.01) by 26.5-53.5%, and the peak plasma concentration (Cmax) was signifi cantly higher (0.4 mg/kg, p<0.05) by 26.2% after oral administration of warfarin with amlodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.26- to 1.53-fold and the absolute bioavailability of warfarin with amlodipine was signifi cantly greater by 61.7-72.5% compared to that in the control group (47.4%). In contrast, amlodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver rather than renal elimination and P-gp by amlodipine.

Stability of Paclitaxel and Vancomycin in 5% Dextrose Injection, 0.9% Sodium Chloride Injection and Hartman's Solution during Simulated Y-site Administration

Jin Pil Burm 한국임상약학회 2001 한국임상약학회지 Vol.11 No.2

Paclitaxel과 vancomycin을 포도당주사액, 염화나트륨주사액 또는 하트만용액과 함께 Y-Site 장치를 써서 환자에게 주입할 때 두 약물의 안정성에 관하며 면구하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml과 vancomycin 1 mg/ml, 5 mg/ml 및 10 mg/ml을 각각 1 : 1로 혼합한 후 0, 1, 2, 4, 12시간 시점에서 두 약물의 농도를 HPLC로 분석하였다, 방해물질에 의한 분석오차를 줄이기 위해 분석법을 여러상태에서 확인하였으며 각 농도에서 3차례씩 실험하였고 각 샘플은 반복하여 HPLC로 분석하였다. 분석전에 각 시료의 투명도, 색의 변화, 침전상태 및 pH를 검사하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml와 vancomycin 1 mg/ml, 5 mg/ml 및 10 mg/mt를 각각 혼합하였을 때 12시간 동안 안정하였으며 주사액의 혼탁이나 색의 변화 및 침전은 나타나지 않았으며 pH도 변하지 않았다.

Stability of 0ndansetron and Fluconazole in 5% Dextrose Injection and Normal Saline during Y-Site Administration

Burm, Jin-Pil The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.2

The stability of ondansetron and fluconazole in 5% dextrose injection and normal saline during simulated Y-site injection at room temperature was studied. Ondansetron 0.03, 0.1 and 0.3 mg/ml were admixed 1:1 with fluconazole 2 mg/ml. The solutions were stored at room temperature and samples were retrieved at time 0, 1, 2, 4 and 12 hr for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, precipitation, and the pH was determined. Drug concentrations were measured by a stability-indicating high performance liquid chromatograph. Ondansetron 0.03, 0.1 and 0.3 mg/ml were stable when mixed with concentration of fluconazole 2 mg/ml. There were no change in clarity and color and no precipitates in any admixture for 12 hr of inspection. The pH measurements did not have a particular trend in any direction over time.

딜티아젬과 아세부토를의 약물상호작용

범진필(Jin Pil Burm),최준식(Jun Shik Choi) 대한약학회 2001 약학회지 Vol.45 No.6

Acebutolol is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism through the gastrointestinal tract and liver. The purpose of this study was to report the pharmacokinetic changes of acebutolol (15 mg/kg, oral) and its main metabolite, diacetolol in rabbits pretreated (15 mg/kg, oral) and coadministered (15 mgtg, S.C., bid for 3 days) with diltiazem. The plasma concentration and area under the plasma concentration-time curves (AUC) of acebutolol and diacetolol were significantly increased in rabbits pretreated and coadministered with dirttiazem. The elimination rate constant (Kel) and total body clearances (CLt) of acebutolol and diacetolol were significantly decreased and ha-life of those were significantly prolonged in the rabbit. Metabolite percentage rate of diacetolol to the plasma concentration of total acebutolol in rabbits pretreated and toadministered with diltiafem were significantly decreased. The results suggest that the dosage of acebutolol should be adiusted when the drug would be administered chronically with diltiazem in a clinical situation.

모집단 약물동태학 방법에 의한 겐타마이신 약물동태에 미치는 환경의 영향

범진필(Jin Pil Burm) 대한약학회 2012 약학회지 Vol.56 No.1

Enviromental differences in gentamicin pharmacokinetics by using population pharmacokinetic methods were compared with 20 Korean patients and 24 Korean-American appendicitis patients. 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 and CV%. The mean K (KS) were 0.402±0.129 h-1 (0.00486±0.00197 [h · ml/min/1.73 m2]-1) and 0.411±0.135 h-1 (0.00475±0.00180 [h · ml/min/1.73 m2]-1) for Korean and Korean-American populations, respectively. The mean V (VS) were not different at 14.3±3.6 l (0.241±0.0511 l/kg) and 15.1±3.84 l (0.239±0.0492 l/kg) for Korean and Korean-American populations, respectively (p>0.2). The mean CL (CS) were 5.68±1.69 l/h (0.0714±0.0222 l/kg [h · ml/min/1.73 m2]) and 5.70±1.77 l/h (0.0701±0.0215 l/kg [h · ml/min/1.73 m2]) for Korean and Korean-American populations, respectively. There were no enviromental differences in gentamicin pharmacokinetics between Korean and Korean-American appendicitis patients.

항결핵약물의 상호작용 (II) 리팜피신과 이소니아짓의 약물상호작용

범진필(Jin Pil Burm),최준식(Jun Shik Choi),이진환(Jin Hwan Lee) 대한약학회 1987 약학회지 Vol.31 No.4

Rifampicin is an indispensable drug along with isoniazid for the control of tuberculosis and is usually prescribed as the combination of rifampicin and isoniazid. This paper is attemped to investigate the interaction of rifampicin and isoniazid. Isoniazid was administered orally at a dose of 30mg/kg of rabbits pretreated with rifampicin 7.5mg/kg, 15mg/kg, and 30mg/kg, respectively twice daily for 9 days. The results are as follows: The blood level and relative bioavailability of isoniazid were decreased significantly (p<0.05) by rifampicin at a dose of 15mg/kg and 30mg/kg. The renal clearance of total isoniazid and ratio of its metabolites to isoniazid were increased significantly (p<0.05) by rifampicin at a dose of 15mg/kg and 30mg/kg. It seemed to be due to enzyme induction by rifampicin. Elimination rate constant (beta) of isoniazid was increased and half life (t1/2beta) was decreased by rifampicin pretreatment. Dosaae regimen of isoniazid after long term administration of rifampicin should be adjusted carefully.