• 약학회지
• /
• 제35권5호
• /
• pp.379-383
• /
• 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.

• Reproductive and Developmental Biology
• /
• 제34권3호
• /
• pp.153-159
• /
• 2010

The 34 potently pig pheromonal odorants (1-32, 5755 & 7113) through structure-based virtual screening and ligand-based virtual screening method were selected and their ADMET and pharmacokinetics characters were evaluated and discussed quantitatively. The pheromonal odorants were projected on the following pre-calculated models, Caco-2 cell permeability, blood-brain barrier permeation, hERG inhibition and volume-distribution. From the results of in silico study, it is found that an optimal compound (31) either penetrating or have a little ($P_{caco2}$=-8.143) for Caco-2 cell permeability, moderate penetrating ability ($P_{BBB}$=0.082) for blood-brain barrier permeation, the low QT prolongation ($P_{hERG}$=1.137) for the hERG $K^+$ channel inhibition, and low distribution into tissues ($P_{VD}$=-5.468) for volume-distribution. Therefore, it is predicted that the compound (31) a topical application may be preferable from these based foundings.

• Biomolecules & Therapeutics
• /
• 제4권3호
• /
• pp.265-270
• /
• 1996

The purpose of this study was to determine pharmacokinetic parameters and tissue distribution patters of urinary trypsin inhibitor(UTI) in Sprague-Dawley rats. $Na^{125}$I was conjugated to UTI to make $^{125}I-UTI$ and the concentrations were determined by $\gamma$-counter. With the aid of nonlinear least-square regression analysis for i.v bolus injection of 1,000 unit UTI including $^{125}I-UTI$, the temporal concentration curves were best fitted by 2-compartment open model. The distribution phase half-life was 0.39$\pm$0.02 hours whereas the elimination half-life was 12.99$\pm$1.05 hours in male rats. The volume of distribution and total body clearance in male rats were 0.28$\pm$0.01 1/kg and 83.16$\pm$1.15 ml/kg/h, respectively. We could not find any difference of pharmacokinetic parameters of UTI between male and female rats. UTI were distributed widely in rat organs. In both male and female rats, the kidney was the highest distributed organ. Amount of UTI in 24 hour cumulative urine in male rats was 36.22$\pm$8.74% and that in 48 hours was 43.32$\pm$10.55%. Excretion via feces was very scanty, with the 24 hours cumulative amount being only 2.76$\pm$0.97%. This data suggest the main excretion route of UTI is urine.

• 한국임상수의학회지
• /
• 제14권2호
• /
• pp.195-200
• /
• 1997

In order to compare the pharmacokinetic profiles of enrofloxacin-HCL)ENFLX-HCL) and enrofloxacin-KOH (ENFLX-KOH) after oral administration in broiler chickens, the study was performed. The chickens used in this study weighed $1.82 {\pm}0.2 kg$ and clinically healthy. The dose of intravenous and lral administration was 5 mg per kg of body weight as enrofloxacin. After intravenous injection of enrofloxacin, it showed two-compartment model with the rapid distribution phase and the slow elimination phase. The mean apparent volume of distribution (Vd) was 2.70 l/kg. The mean half-life of elimination and distribution showed 8.26 h and 0.44 h, respectively. The mean area under curve (AUC) was calculated as $19.7 {\mu} g{\cdot} h/ml$. After oral administration of ENFLX-HCL and ENFLX-KOH with a rate of dose 5 mg of enrofloxacin/kg of body weight, Both of the products were showed one-compartment model unlike that of i.v. enrofloxacin standard solution showed the mean bioavailability of 79.64% for the ENFLX-KOG and 86.24% for the ENFLX-HCL. The mean total body clearance of the former was 0.24 l/kg/h and the latter 0.42 l/kg/h. Both enorfloxacin formulations seemed to have good tissue distribution and penetration as indicated by large volume of distribution : 2.72 l/kg for the -KOH and 4.44 l/kg for the -HCL. With the results obtained in this study, ENFLX-HCL could be used in place of its salt form in chickens.

• Biomolecules & Therapeutics
• /
• 제5권2호
• /
• pp.179-186
• /
• 1997

The pharmacokinetics and tissue distribution of DWP20373, a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20373 in plasma, tissue, and urine was performed by both HPLC and microbiological assay. The plasma drug concentration declined biexponentially both rats and beagle dogs. In the rats, the terminal drug elimination half-life (t$_{1}$2$\beta$/) was 64 min (IV) and 57 min (PO) by bioassay, and 76 min (IV) and 77 min (PO) by HPLC. Whereas in beagle dogs, t$_{1}$2$\beta$/ was 196 min (IV) and 350 min (PO). The volume of distribution at steady-state (Vd$_{ss}$ ) was 811 ml/kg (bioassay) and 2061 ml/kg (HPLC) in rats, and 2738 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20373 was 10 ml/min/kg (bioassay) and 7 ml/min/kg (HPLC) in rats, and 11 m1/min/kg (bioassay) in beagle dogs. The extent of bioavailability after oral administration was 49% (bioassay) and 67% (HPLC) in rats, and 84% (bioassay) in beagle dogs. The 24-h urinary recovery, measured by bioassay, was 2.7% after oral dosing and 5.5% after intravenous dosing in rats. Serum protein binding ratio determined at 27g/ml was 78%. This drug was also distributed in tissues in the decreasing order of liver, kidney, spleen, lung, heart, and muscle determined at 30 min after oral administration.on.

• Journal of Pharmaceutical Investigation
• /
• 제35권5호
• /
• pp.349-353
• /
• 2005

This study reports the pharmacokinetics of a novel histone deacetylase inhibitor, SD-0542, in rats after i..v. and oral administration. SD-0542 was injected intravenously at doses of 10, 20, and 40 mg/kg. The terminal elimination half-life $(t_{1/2})$, systemic clearance (Cl), and steady-state volume of distribution $(V_{ss})$ remained unaltered as a function of dose, with their values ranging from 2.0-2.5 hr, 157.2-214.1 ml/min/kg, and 11.1-17.5 L/kg, respectively, whereas, the initial serum concentration $(C_0)$ and AUC increased linearly as the dose was increased. Renal excretion of SD-0542 was minimal. Oral pharmacokinetic studies were conducted in rats at a dose of 20 mg/kg. The $T_{max}$, Cl/F, $V_{z}/F$, and $t_{1/2}$ were 2.0 hr, 92864 ml/min/kg, 16331 L/kg, and 2.0 hr, respectively. Taken together, SD-0542 showed linear pharmacokinetics over the i.v. bolus dose range studied. SD-0542 was poorly absorbed, with the absolute oral bioavailability of 0.9%.

• 약학회지
• /
• 제46권1호
• /
• pp.63-68
• /
• 2002

The purpose of this study was to estimate the population pharmacokinetics of clarithromycin in healthy adult Korean and to investigate the factors influencing the pharmacokinetics of clarithromycin. The population pharmacokinetic parameters of clarithromycin were calculated with the data from healthy adult Koreans. A total of 798 plasma concentrations obtained from 78 subjects after administration of a single oral dose of 250 mg or 500 mg were used for the modeling. The concentration-time data were fitted to a one-compartment open model assuming a first-order absorption and elimination with no lag time. The correlations between various factors [such as sex, age, height, weight, sect creatinine (Scr) and dose and pharmacokinetic parameters were estimated with stepwise linear recession analyses. The selected covariates were incorporated in the population model of NONMEM, and the importance of each covariate was investigated by means of backwards elimination. The apparent clearance (CL/F) was significantly correlated to Scr and sex, and the apparent volume of distribution (Vd/F) was significantly correlated to Scr and height in a nonlinear relationship. The population values of Ka was 1.8 h $r_{-1}$, CL/F was 37.71 L/hr, Vd/F was 200 L and t/ sub 1/2 / was 3.68 hrs for a male Korean with 170 m height and 1.0 mg/dL Scr.

• 약학회지
• /
• 제44권3호
• /
• pp.245-250
• /
• 2000

Because nonsteroidal anti-inflammatory drugs are reported to cause fluid retention and hypertension by inhibition of prostaglandin synthesis, the effects of piroxicam on pharmacodynamics and pharmacokinetics of nifedipine were studied in male spontaneously hypertensive rats. They received nifedipine (0.5 mg/kg) alone or combined with piroxicam (5 mg/kg) intravenously. Plasma levels norepinephrine, an index of sympathetic stimulation, were measured prior to each treatment and 5 min after drug administration. Changes in blood pressure were examined serially and blood samples for analysis of nifedipine were also taken for 6 hr following drug administration. Plasma nifedipine concentration were assayed by HPLC and pharmacokinetic parameters were calculated. Blood pressure was reduced (p<0.01), but plasma norepinephrine level was increased (p<0.05) by nifedipine administration. Anti-hypertensive effect of nifedipine was potentiated (p<0.05) by piroxicam coadministration, but effect of nifedipine on plasma norepinephrine level was not affected. In case of rats received nifedipine and piroxicam, plasma nifedipine concentrations were higher (p<0.05) than those from rats received nifedipine alone at 2,3,4,5 and 6 hours following drug administration. The area under the plasma concentration vs. time curve was increased (p<0.05), while the elimination rate constant was decreased (p<0.01) by piroxicam coadministration. No significant differences were observed in the plasma clearance, apparent volume of distribution and elimination half-life. Thus, piroxicam not only potentiated antihypertensive effect of nifedipine, but also altered nifedipine pharmacokinetics in the rats. It is concluded that the potentiation of nifedipine antihypertensive effect might correlate with the increment of its plasma concentration by piroxicam coadministration.

• The Korean Journal of Physiology and Pharmacology
• /
• 제8권1호
• /
• pp.65-67
• /
• 2004

Dehydroevodiamine (DHED) is one of the bioactive components of the Chinese herbal medicine Wu-chu-yu-tang that has been shown to produce various pharmacological effects. In the present study, we investigated the pharmacokinetics of DHED after intravenous administration of two doses (2.5 and 5 mg/kg) in anesthetized rats. The plasma concentration of DHED was measured by reverse-phase high-performance liquid chromatography with UV detection. The mean area under the curve of the time-concentration profile was $21.9\;and\;53.9\;{\mu}g{\cdot}min/ml$ after the 2.5- and 5-mg/kg doses, respectively, and the volume of distribution was 1584.9 and 1580.6 ml following 2.5- and 5-mg/kg doses, respectively. Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. The terminal elimination half-life was $91.8{\pm}16.6\;min$ and $78.7{\pm}11.9\;min$ in the dose of 2.5 and 5 mg/kg, respectively. This is the first report to study the pharmacokinetics of DHED in animals.

• Biomolecules & Therapeutics
• /
• 제8권2호
• /
• pp.171-178
• /
• 2000

To evaluate the pharmacokinetic properties and tissue distribution of a newly developed recombinant human erythropoietin (GC-rhEPO), we analyzed the plasma and tissue levels of erythropoietin by an ELISA after intravenous (IV) and subcutaneous (SC) adminstration to the male rats at the doses of 20, 100, 500 or 2,500 unit/kg. After single IV bolus injection of GC-rhEPO, the plasma concentration was rapidly increased and decreased with two phases with half-lives of 13.4 min and 2.94 hours. AUC was increased dose- dependently but plasma half-lives remained constant regardless of GC-rhEPO doses. Following SC administration, the plasma concentration increased slowly with half-life of 9.2 hours and reached peak at 8 hours. Mean residence time and bioavailability were 18.2 hours and 44%, respectively. After single IV dose of 100 unit/kg, tissue GC-rhEPO level was higher in bone marrow and spleen, while the depletion rate was slower in liver and bone marrow, indicating the higher affinity of GC-rhEPO to bone marrow. Taken together, the experimental results indicate that GC-rhEPO contained the typical pharmacokinetic properties and the tissue distribution patterns inherent to human erythropoietin.