• YAKHAK HOEJI
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• v.41 no.3
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• pp.312-320
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• 1997

Pharmacokinetics and tissue distribution of DWP20349 and 20351, new quinolones, were examined in rats after a single intravenous and oral administration. Analyses of DWP20349 an d DWP20351 in plasma, tissue, and urine were determined by both HPLC and bioassay(microbiological assay). The plasma concentrations of the drugs declined biexponentially. The terminal half-lives ($t_{1/2\beta}$) of drugs were about 114 min (DWP20349) and 105 min (DWP20351) after intravenous dosing, and were 77 min (DWP20349) and 79 min (DWP20351) after oral dosing. The volume of distrbution at steady-state ($Vd_{ss}$) and total body clearances ($Cl_t$) of DWP20349 and DWP20351 were 760 ml/kg and 1126 ml/kg, and 5ml/min/kg and 10 ml/min/kg, respectively. The extents of bioavailability if DWP20349 and DWP20351 after oral administration were 29% and 28%, respectively. 24 h urinary recoveries measured by bioassay were 1.8% (DWP20349) and 1.3% (DWP20351) after oral dosing, and 2.4% (DWP20349) and 1.9% (DWP20351) after intravenous dosing. Plasma protein binding ratios ranged from 87%-90% (DWP20349) and 61%-68% (DWP20351). These drugs were highly distrbuted by the order of lung, kidney, liver and plasma (DWP20394), and lung, liver, kidney and plasma (DWP20351) after 1 hour orally administered.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.419-425
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• 1997

The pharmacokinetics of DWP20364 (1-cyclopropyl -5-amino-6,8-difluoro-7-(2,7-diazabiclo [3,3,0] oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone containing C7-bicyc-talc structure, were compared with those of ciprofloxacin (CPFX) after single intravenous (i.v.) and oral (p.o.) administration to rats using microbiological assay (bioassay). After i.v. administration to rats, the plasma concentrations of the two drugs declined biexponentially. The terminal half-lives (t$_{1}$2$\beta$/) of DWP20364 were 110$\pm$ 13.2 min and 117$\pm$3.09 min after i.v. and p.o. administration, respectively, and they were significantly higher than those of CPFX (45.5$\pm$9.52 min and 48.3$\pm$ 12.1 min, respectively). Similar results were also obtained from plasma concentrations and area under the plasma concentration-time curves. The total body clearance of DWP20364, 7.82$\pm$0.37 ml/min/kg was significantly slower than that of CPFX, 27.3 $\pm$ 11.1 m1/ min/kg. Above data suggested that the antimicrobial activity of DWP20364 could be longer than that of CPFX. The urinary recovery after i.v. and p.o. administration of DWP20364 was significantly lower than those of CPFX suggesting that the effect of DWP20364 on urinary tract infection could be lower than that of CPFX. The serum protein binding values of DWP20364 at 2$\mu$g/ml were apparently 91.5~93.1% in rats and human. DWP20364 was distributed by the order of liver, lung, kidney, sf)leon, heart, muscle and brain collected at 30 min after orally administered.

• Archives of Pharmacal Research
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• v.19 no.5
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• pp.359-367
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• 1996

The pharmacokinetics of LB20304 was investigated following intravenous (IV) and oral administration to rats and dogs. Additionally, in vitro metabolism and serum protein binding studies were also conducted. The total body clearance, apparent volume of distribution, terminal half-life, and extent of bioavailability were 21.8 ml/min/kg, 2265 ml/kg, 93.6 min, and 30.8% for rats; and 7.95 ml/min/kg, 4144 ml/kg, 363 min, and 81.1% for dogs, respectively. LB20304 was stable in the liver microsome containing NADPH generating system and its serum protein binding was 58.5-65.8% for rats, 19.1-29.6% for dogs, and 56.9-59.6% for humans. Its tissue concentration levels in lever, stomach, small intestine, and kidney were 9.5 to 26.1 times greater than plasma level, but the concentration in testis was quite low and that in brain was negligible in rats. The 48 hr urinary recovery of the dose was 44% for IV dosing and 14% for oral dosing, shereas the 48 hr biliary recovery of the dose was 6.4% for IV dosing and 4.5% for oral dosing in rats. In summary, the pharmacokinetic properties of LB20304 were characterized by its good oral absorption, long plasma half-life, and good tissue distribution.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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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.

• Korean Journal of Clinical Pharmacy
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• v.18 no.1
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• pp.60-67
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• 2008

This study aimed to compare a microparticle enzyme immunoassay (MEIA) with a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for the measurement of tacrolimus concentrations in adult liver transplant recipients, to investigate how the assay choice influenced the population pharmacokinetics of tacrolimus and to identify patient characteristics that affected pharmacokinetic parameters in each assay. Tacrolimus concentrations from 29 liver (n=52 paired-samples) transplant recipients measured by both MEIA and LC/MS/MS were used to evaluate the performance of these methods in the clinical setting. Tacrolimus pharmacokinetics was studied independently using MEIA and LC/MS/MS data in 70 adult patients using a population approach performed with NONMEM. Patient characteristics which influenced pharmacokinetic parameters in each assay were compared. The relation between LC/MS/MS and MEIA measurements was best described by the regression equation MEIA=1.465*LC/MS/MS-1.336 (r=0.91). Multiple linear regression analysis showed significant inverse relationships between assay difference and hematocrit (Hct) (p<0.025) in liver graft recipients. In MEIA, the population estimate of tacrolimus CL/F and apparent volume of distribution (Vd/F) were found to be 10.1 L/h and 226 L, and in LC/MS/MS, 13 L/h and 305 L respectively. Neither patient's age, weight, gender, grafted hepatic weight, albumin concentration, nor markers of liver function influenced tacrolimus CL/F The final model of CL/F was found to be 10.1+(Hct/Hct mean)$^{12.0}$ in MEIA and 13+(1+Hct/578) in LC/MS/MS indicating that CL/F was influenced by hematocrit.

• YAKHAK HOEJI
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• v.56 no.1
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• pp.48-54
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• 2012

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 ($C_{cr}$), 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 $C_{cr}$ and the V. The output includes two marginal probability density function (PDF), means, medians, modes, variance and CV%. The mean K (KS) were $0.402{\pm}0.129\;h^{-1}(0.00486{\pm}0.00197\;[h{\cdot}ml/min/1.73\;m^2]^{-1})$ and $0.411{\pm}0.135\;h^{-1}(0.00475{\pm}0.00180\;[h{\cdot}ml/min/1.73\;m^2]^{-1})$ for Korean and Korean-American populations, respectively. The mean V (VS) were not different at $14.3{\pm}3.6l(0.241{\pm}0.0511l/kg)$ and $15.1{\pm}3.84l(0.239{\pm}0.0492l/kg)$ for Korean and Korean-American populations, respectively (p>0.2). The mean CL (CS) were $5.68{\pm}1.69l/h(0.0714{\pm}0.0222l/kg[h{\cdot}ml/min/1.73\;m^2])$ and $5.70{\pm}1.77l/h(0.0701{\pm}0.0215l/kg[h{\cdot}ml/min/1.73\;m^2])$ for Korean and Korean-American populations, respectively. There were no enviromental differences in gentamicin pharmacokinetics between Korean and Korean-American appendicitis patients.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.103-112
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• 1995

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 constant(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$\pm$0.139(0.00429$\pm$0.00164) and 0.411$\pm$0.135 hr$^{-1}$ (0.00475$\pm$0.00180[hr.mL/min/1.73m$^{2}]^{-1}$) for American and Korean-American populations, respectively. The mean V(VS) were not different at 15.6$\pm$4.77(0.233$\pm$0.0526) and 15.1$\pm$3.84L(0.239$\pm$0.0492 L/kg) for American and Korean-American populations, respectively (P>0.2). The mean CL (CS) were 6.28$\pm$1.85(0.0634$\pm$0.0191) and 5.70$\pm$1.77 L/hr(0.0701$\pm$0.0215 L/kg[hr.mL/min/1.73m$^{2}$)] for American and Korean-American populations, respectively. There are no differences in gentamicin pharmacokinetics between American and Korean-American Appendicitis patients.

• Korean Journal of Clinical Pharmacy
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• v.3 no.2
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• pp.139-145
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• 1993

This study was attempted to investigate the pharmacokinetics of phenytoin(4mg/kg iv,) in rabbits pretreated with diltiazem(l and 2.5mg/kg) for 7 days. The plasma concentration and area under the curve(AUC) of phenytoin were increased significantly(p<0.05) in rabbits pretreated with diltiazem(2.5mg/kg) compared with those of control rabbits. Volume of distribution and total body clearance were decreased significantly(p<0,05) in rabbits pretreated with diltiazem compared with those of control rabbits. From the results of this experiment, it is desirable that dosage ragimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin will be administered with diltiazem in clinical practice.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.287-287
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• 1996

Long-circulating liposomes have prompted interests in using them as a drug delivery system. This improvements in delivery has been thought to be the results from sustained action of liposomes in plasma without RES uptake. Although methotrexate(MTX) has been one of the most widely used antineoplastc drug, its use was limited by prompt RES uptake. The purpose of this study was to prepare long-circulating liposomes for MTX using highly water-soluble polymer (PEG-PE). In vitro, release of MTX from liposomes in phosphate buffer (pH 7.4), rat liver homogenate, and rat plasma was investigated. The pharmacokinetics and organ distribution of fee drug, conventional and long-circulating liposomes were also compared with one another after intravenous administration to rats.

• Toxicological Research
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• v.7 no.1
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• pp.37-46
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• 1991

To evaluate the influence of ochratoxin A on the pharmarcokinetics of gentamicin, gentamicin concentrations in the serum, renal cortex and medulla together with parameters of the renal function and histological changes were compared between ochratoxin A-treated rats (0.1 mg of ochratoxin A/kg of body weight, ip, daily for 14 days) and normal rats. Gentamicin was given with a single intramuscular injection (10mg/kg of body weight). Ochratoxin A resulted in an increase of the half-life, the area under the concentration-time curve, the apparent volume of distribution and a decrease of the total body clearance of gentamicin, and accumulated significantly (p<0.01) more gentamicin in the kidneys.