Stability of Paclitaxel with Cephalosporines in $0.9\%$ Sodium Chloride Injection and $5\%$ Dextrose Injection During Simulated Y-Site Administration

범진필,Burm, Jin Pil Korean College Of Clinical Pharmacy 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 $5\%$포도당주사액 그리고 $0.9\%$ 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.

Stability of Taxol and Ondansetron Hydrochloride in $5\%$ Dextrose Injection and $0.9\%$ Sodium Chloride Injection during Simulated Y-Site Administration

범진필,Burm, Jin Pil Korean College Of Clinical Pharmacy 2000 한국임상약학회지 Vol.10 No.2

Y-Site 투여시 $5\%$포도당액과 생리식염수에서 탁솔과 은단세트론의 안정성에 관해 실온과 형광등 아래서 연구하였다. 온단세트론 0.03 mg/ml, 0.1 mg/ml, 0.3 mg/ml와 탁솔 0.3 mg/ml, 1.2mg/ml를 각각 1:1로 혼합한 후 0, 1, 2, 4, 12시간에서 즉시 약물농도를 HPLC로 분석하였다. 방해물질에 의한 분석오차를 줄이기 위해 분석법을 여러상태에서 확인하였으며, 각 농도에서 3차례씩 실험하였고 각 샘플은 2차례 연속 HPLC 분석하였다. 분석전에 각 시료의 투명도, 색의변화, 침전상태 및 pH를 검사하였다. 온단세트론 0.03, 0.1 및 0.3 mg/ml와 탁솔 0.3 및 1.2mg/ml를 각각 혼합하였을 때 12시간 동안 안정성이 있었다. 혼탁이나 색의 변화 및 침전은 나타나지 않았으며 12시간 동안 pH의 변화는 특별한 경향이 없었다.

비모수적 기대최대치(NPEM) 연산방법에 의한 미국인과 재미동포 충수돌기염 환자에게 겐타마이신의 모집단 약물동태학

범진필(Jin Pil Burm),최준식(Jun Shik Choi),Stanford Jhee,Mark A. Gill 대한약학회 1995 약학회지 Vol.39 No.2

Population pharmacokinetics for gentamicin were compared with 24 American patients (16 male and 8 female) and 16 Korean-American appendicitis patients(12 male and 4 female). Two to six blood specimens were collected from all patients at the following times: just before a regularly scheduled infusion and at 1/2 hour after the end of a 1/2 hour infusion. Nonparametric expected maximum(NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constants(K), the slope of the relationship between K versus creatinine clearance(KS), the apparent volume of distribution(V), the slope of the relationship between V versus weight(VS), gentamicin clearance(CL) and the slope of the relationship between CL versus creatinine clearance and the VS(CS). The output includes a 3-dimensional plot of the joint probability density function(PDF), two marginal PDF, means, medians, modes, variance, skewness, kurtosis, and CV%. The mean K(KS) were 0.424 +/- 0.139(0.00429 +/- 0.00164) and 0.411 +/- 0.135 hr-1 (0.00475 +/- 0.00180[hr.mL/min/1.73 m2]-1) for American and Korean-American populations, respectively. The mean V(VS) were not different at 15.6 +/- 4.77(0.233 +/- 0.0526) and 15.1 +/- 3.84L(O.239 +/- 0.0492L/kg) for American and Korean-American populations, respectively (P>0.2). The mean CL(CS) were 6.28 +/- 1.85(0.0634 +/- 0.0191) and 5.70 +/- 1.77L/hr(0.0701 +/- 0.0215L/kg[hr.mL/min/1.73m2]) for American and Korean-American populations, respectively. There are no differences in gentamicin pharmacokinetics between American and Korean-American appendicitis patients.

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.

리팜피신과 이소니아짓의 약물상호작용

범진필(Jin Pil Burm),최준식(Jun Shik Choi) 대한약학회 1986 약학회지 Vol.30 No.5

Rifampicin suspension was administered orally at a does of 34mg/kg to six rabbits after 5, 10 and 20mg/kg pretreatment of isoniazid twice daily for 9 days. The blood level of rifampicin was decreased significantly by isoniazid 10mg/kg, 20mg/kg pretreatment. The renal clearance(CLr) of rifampicin was increased by isoniazid 20mg/kg and the biliary clearance(CLb) was increased by isoniazid 10mg/kg and 20mg/kg pretreatment. Elimination rate constant(K) and time to reach maximum concentration(tmax) were increased by isoniazid pretreatment. But half-life and maximum concentration(Cmax) were decreased. Relative bioavailability was decreased significantly by isoniazid 10mg/kg and 20mg/kg pretreatment.

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.

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.

엽산으로 유도된 신장장애 가토에서 정맥투여시 딜터아젬과 활성대사체인 데아세델딜터아젬의 약물동태

최준식,범진필,Choi, Jun Shik,Burm, Jin Pil 한국임상약학회 2000 한국임상약학회지 Vol.10 No.3

Diltiazem inhibits calcium channels and leads to vascular smooth muscle relaxation and negative inotroic and chronotropic effects in the heart. Diltiazem (DTZ) is almost completely absorbed after oral administration, but its bioavailability is reduced because of considerable hepatic first-pass metabolism. The main metabolite of DTZ is deacetyldiltiazem. The purpose of this study was to report the pharmacokinetic changes of DTZ and its metabolite, deacetyldiltiazem (DAD) after intravenous administration of diltiazem to control rabbits and rabbits with mild and medium folate-induced renal failure (FIRRs). The area under the plasma concentration-time curves (AUC) of DTZ were significantly increased in mild and medium FIRRs. The metabolite ratio of the DAD to DTZ were significantly decreased in mild and medium FIRRs. The elimination rate constant $(\beta)$ and total body clearances (CLt) of DTZ were significantly decreased in mild and medium FIRRS. These findings suggest that the hepatic metabolism of diltiazem was inhibited and CLt and ${\beta}$ of DTZ were significantly decreased in mild and in rabbits with medium folate-induced renal failure.

세파졸린의 경구투여를 위한 프로드럭의 개발 -세파졸린 에톡시카보널에칠 에스텔의 합성, 분배계수 및 항균력-

정영국,범진필,최준식,이진환,Jung, Young-Guk,Burm, Jin-Pil,Choi, Jun-Shik,Lee, Jin-Hwan 한국약제학회 1994 Journal of Pharmaceutical Investigation Vol.24 No.4

Cefazolin ethoxycarbonylethyl ester (CFZ-ET) was synthesized to improve oral absorption and bioavailability of the parent drug by esterification of sodium cefazolin (CFZ-Na). The successful synthesis of CFZ-ET was identified with analysis of UV spectra, FT-lR spectra and NMR spectra. Partition coefficient studies showed that CFZ-ET was more lipophilic than CFZ-Na and the ester was hydrolyzed into the parent drug in vivo. Although CFZ-ET did not have antimicrobial activity in vitro, the plasma taken after the oral administration of CFZ-ET had antimicrobial activity. Based on above observations, CFZ-ET might be rapidly hydrolyzed to CFZ in the body. Therefore, it may be concluded that CFZ-ET could be a novel prodrug of CFZ which can improve the bioavailability of CFZ-Na.

리팜피신 제제의 생물학적 동등성시험(제2보)

장일효,범진필,최준식,Chang, Il-Hyo,Burm, Jin-Pil,Choi, Jun-Shik 한국약제학회 1994 Journal of Pharmaceutical Investigation Vol.24 No.2

Bioequivalence test of commercially available rifampicin capsules was performed. Sixteen volunteers were divided into 2 groups and the reference and test drug were given orally (450 mg) by cross-over design. Statistical evaluation of AUC, $C_{max}\;and\;T_{max}$ involved an analysis of variance (ANOVA). The differences of mean value in AUC, $C_{max}\;and\;T_{max}$ between the reference and test drug were within 20% with reference drug. ANOVA showed no significant differences for ‘between group’, ‘drug’ and ‘period’, but not for ‘between subjects’. The power of test $(1-{\beta})\;of\;AUC\;and\;$C_{max}$ was larger than 0.8 and the confidence of bioavailability was $within\;{\pm}20%$. From these results, it was concluded that the two preparations were bioequivalent for AUC and $C_{max}$, but was not for $T_{max}$.