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.

위암 환자에서 반코마이신의 임상약물동태

최준식,장일효,범진필,Choi, Jun-Shik,Chang, Il-Hyo,Burm, Jin-Pil 대한약학회 1997 약학회지 Vol.41 No.2

The purpose of this study was to determine pharmacokinetic parameters of vancomycin using two point calculation(TPC) and Bayesian methods in 16 Korean normal volunteers and 15 g astric cancer patients. Nonparametric expected maximum(NPEM) algorithm for calculation of population pharmacokinetic parameter was used, and these parameters were applied for clinical pharmacokinetic parameters by Bayesian analysis. Vancomycin was administered 1.0g every 12 hrs for 3 days by IV infusion over 60 minutes. The volume of distribution(Vd), elimination rate constant(Kel) and total body clearance(CLt) of vancomycin in normal volunteers using TPC method were $0.34{\pm}0.06 L/kg,\; 0.19{\pm}0.01 hr^{-1}$ and $4.08 {\pm} 0.93 L/hr$, respectively, The Vd, Kel and CLt of vancomycin in gastric cancer patients using TPC method were $0.46 {\pm} 0.06 L/kg, 0.17{\pm}0.02 hr^{-1}$ and $4.84 {\pm} 0.57 L/hr$ respectively. There were significant differences(p<0.05) in Vd. Kel and CLt between normal volunteers and gastric cancer patients. Polpulation pharmacokinetic parameter, the slope(KS) of the relationship beetween Kel versus creatinine Clearance, and the Vd were $0.00157{\pm}0.00029(hr{\cdot}mL/min/1.73m^2)^{-1},\; 0.631 {\pm} 0.0036 L/kg$ in gastric cancer patients using NPEM algorithm respectively. The Vd and Kel were $0.63{\pm}0.005 L/kg, 0.15 {\pm}0.027 hr^{-1}$ for gastric cancer patients using Bayesian method. There were significant differences(p<0.05) in vancomycin pharmacokinetics between Bayesian and TPC methods. It is considered that the population parameter in the patient population is necessary for effective Bayesian method in clinical pharmacy practise.

간장장애 가토에서 베라파밀의 약물동태

최준식,김형중,Choi, Jun-Shik,Kim, Hyung-Jung 한국임상약학회 2004 한국임상약학회지 Vol.14 No.1

The purpose of this study was to investigate the pharmacokinetic changes of verapamil in rabbits with hepatic disorder induced by carbon tetrachloride. The plasma concentrations of verapamil were increased significantly (p<0.05, in slight group; P<0.01, in moderate and severe group) in all groups of hepatic disorder compared to the control group. Morover, the $C_{max}\;in\;slight\;(77.9\%$ increase), moderate ($110\%$ increase), and severe ($174\%$ increase) hepatic disorder groups were significantly (p<0.05, in slight; p<0.01, in moderate and severe) higher than that in control rabbits. These resulted in significantly (p<0.05, in slight; p<0.01, in moderate and severe) greater area under the plasma concentration-time curve (AUC) in moderate ($49.8\%$ increase), moderate ($95.0\%$ increase), and severe ($144\%$ increase) hepatic disorder groups than that in control rabbits. Hence, the relative bioavailability values were 149, 195, and $244\%$ for slight, moderate, and severe hepatic disorder groups, respectively. This could be due to decrease in metabolism of verapamil in the liver because of suppressed hepatic function in the hepatic disorder groups because verapamil is mainly metabolized in the liver.

Probenecid와 Nalidixic Acid의 약물상호작용(藥物相互作用) ( II )

최준식,이진환,김용현,이민화,Choi, Jun-Shik,Lee, Jin-Hwan,Kim, Yong-Hyun,Lee, Min-Hwa 한국약제학회 1983 Journal of Pharmaceutical Investigation Vol.13 No.4

The interaction between probencid and nalidixic acid was studied pharmacokinetically in rabbits infused with or without acidic soiution (5% $NH_4Cl$). The results were as fellows. The blood level and the area under the blood concentration curve of nalidixic acid administered intravenously was elevated by coadministration of probenecid and more elevated in rabbits infused with acidic solution. Probenecid inhibited the urinary excretion of nalidixic acid in rabbits infused with adidic solution. Therefore, biolgcal half-life of nalidixic acid was prolonged by coadministration of probencid.

푸로푸라놀롤과 안지오텐신 차단제와의 체내 상호작용

최준식,이진환,범진필,Choi, Jun-Shik,Lee, Jin-Hwan,Burm, Jin-Pil 한국약제학회 1990 Journal of Pharmaceutical Investigation Vol.20 No.1

Effect of an angiotensin inhibitor (AAS; loading dose of 25, 50, $100{\mu}g/kg$ and maintenance dose of 12.5, 25,$50{\mu}g/ka/hr$) on the pharmacokinetics of propranolol (4 mg/kg i.v.) was studied in rabbits. Plasma concentrations and relative bioavailability of propranolal increased upto 127-175% by AAS coinjection. The urinary excretion of propranolol decreased by AAS. Dosage regimen of propranolol should be adjusted when it is administered with AAS.

시판 이소니아짓 정제의 생물학적 동등성시험에 관한 연구

최준식,안선엽,Choi, Jun-Shik,An, Seon-Yeob 대한약학회 1989 약학회지 Vol.33 No.4

Even though two different preparations are chemically equivalent, the variance of bioavailability differenciates the clinical effect of preparations, so that the preparations need to be evaluated by comparing bioavailability in vivo as well as chemical equivalence. In this study, bioequivalence tests of commercially available isoniazid tablets A, B, C and D (standard) were performed to give some guidelines to bioequivalence test. The bioavailability parameters obtained by drug administeration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance for a cross over design. Cross over design was employed with 8 healthy volunteers. The results were within 20% difference of mean value in the AUC, Cmax, Tmax and amount of urinary excretion (Au) between standard and isoniazid tablets. The results of ANOVA showed no significant differences for 'group or sequence', but almost not for 'between subjects'. The tablet. A, B and D were within 20 min, but tablet C was within 50 min. Tablet A was biologically equivalent in the Au. tablet B biologically equivalent in the Au and AUC. Tablet C was biologically equivalent in the Au. The relationship between the dissolution rate and Au was significant.

신장장애 가토에서 경구투여시 아세부토롤과 활성대사체인 디아세토롤의 약물동태

최준식(Jun Shik Choi),이진환(Jin Hwan Lee) 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.3

N/A Acebutolol (ABT) is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism in the gastrointestine and liver. The purpose of this study was to report the pharmacokinetic changes of ABT and its metabolite, diacetolol (DAT) after oral administration of acebutolol to control rabbits and rabbits with mild and severe folate-induced renal failure (FIRRs). Both of the area under the plasma concentration-time curve (AUC^0_∞) of ABT and DAT were significantly increased in mild (p<0.05) and severe FIRRs (p<0.01), but the AUC^0_∞ of DAT was more influenced than that of ABT in severe rabbits. There was a good correlation between serum creatinine and both of AUC^0_∞ of ABT and DAT. The elimination half-life of ABT and DAT was significantly prolonged in mild (p<0.05) and severe (p<0.01) FIRRs, but the half-life of DAT was more influenced than that of ABT in severe FIRRs. The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal disorder on the base of the serum creatinine concentration.

사염화탄소 및 담도폐쇄 유발 간장장애 가토에서 싸이크로스포린의 약물동태

최준식(Jun Shik Choi),최병철(Byong Chul Choi),범진필(Jin Pil Burm) 대한약학회 1998 약학회지 Vol.42 No.2

This study was attempted to investigate the pharmacokinetics of cyclosporine (10mg/kg, oral) in rabbits with CC14 and bile duct ligation-induced hepatic disorder. The area under the curve (AUC) of blood cyclosporine concentration versus time was significantly increased (p4-induced hepatic disorder. Elimination rate constant (Kel) was significantly decreased (p<0.05, p<0.01) in rabbits with CC14 and bile duct ligation-induced hepatic disorder. Volume of distribution (Vdss) and total body clearance (CLtot) were significantly decreased (p<0.01) in rabbits with CC14-induced hepatic disorder. But Vdss was significantly increased (p4-induced hepatic disorder were 874ng/ml and 2.71 hr, respectively. Cmax and Tmax values in rabbits with bile duct ligation were 105ng/ml and 2.834 hr, respectively. From results of this experiment. It is desirable to do therapeutic drug monitoring of cyclosporine for effective treatment when the cyclosporine is administered to patients with liver disorder m clinical practice.

토끼에서 체내담즙이 아세부톨를의 생체이용률 및 체내동태에 미치는 영향

최준식(Jun Shik Choi) 대한약학회 2002 약학회지 Vol.46 No.1

Although acebutolol (ABT) is almost completely absorbed in the gastrointestinal (GI) tract, oral bioavailability of the drug is low due to extensive first-pass metabolism in the Gl tract and liver, In the present study; bioavailability and pharmacokinetics of ABT was studied in bile duct-bypassed rabbits after oral administration. For ABT the time to reach the plasma peak (Tmax) and mean resident time (MRT) were increased by the treatment. For diacetolol (DAT), a metabolite of ABT area under the plasma concentration-time curve (AUC), T max and plasma half-life were increased by the treatment. These results indicate that oral bioavailability of ABT is associated with the enterohepatic recycling of bile juice components.

세프라딘 캅셀(세프라딘 250 mg)의 생물학적 동등성

최준식(Jun Shik Choi),이진환(Jin Hwan Lee),박영진(Young Jin Park),범진필(Jin Pil Burm) 대한약학회 2002 약학회지 Vol.46 No.4

Cephradine is an orally absorbed cephalosporin with a broad spectrum of activity against gram-positive and gram-negative bacteria and is highly resistant to beta- lactamase degradation. The purpose of the present study was to evaluate the bioequivalence of two cephradine capules, Cephradine capsule (Donggu Pharmaceutical Co., reference drug) and Cephradine capsule (Shinpoong Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration. Lrenty-six normal volunteers,24.6 +/- 3.70 years in age and 62.4 7 +/- 8.99 kg in body weight, were divided into two groups and a randomized 2 x 2 cross-over study was employed. After one capsule containing 250 mg of cephrdine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephrdine in serum were deter- mined using HPLC with UV detector, The pharmacokinetic parameters such as AUC1, Cmax And Tmax were calculated and ANOYA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUCt,Cmax and Tme between two products were 2.89%, 1.05% and 1.06%, respective1y; when calculated against the reference drug. The 90% confidence intervals were within log0.8 ≤ δ ≤ log1.25 (e.g., log0.9803 ≤ δ ≤ log1.0734 and logo.9674 ≤ δ≤log1.220 for AUCt, and Cmax, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Cephradine capsules (Shinpoong Pharmaceutical Co.) is bioequivalent to Cephradine capsules (Donggu Pharmaceutical Co.).