• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.331-334
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• 2008

The objectives of this study were to formulate oral paclitaxel microemulsion and to compare the bioavailability of paclitaxel in the microemulsion formulation from the commercially available $Taxol^{(R)}$ formulation. Paclitaxel microemulsion was formulated with much less amount of Cremophor $EL^{TM}$ as compared with $Taxol^{(R)}$ to reduce severe adverse reactions produced by Cremophor $EL^{TM}$. The area under the plasma concentration-time curve from 0 hr to 24 hr ($AUC_{0-24}$), maximum plasma concentration ($C_{max}$), and relative bioavailability of palcitaxel microemulsion were increased as compared with $Taxol^{(R)}$ after oral administration. The time required to reach $C_{max}\;(T_{max})$ of palcitaxel microemulsion was significantly shorter than $Taxol^{(R)}$ following oral administration. These results suggest the faster intestinal absorption and the enhanced oral bioavailability of paclitaxel in the microemulsion formulation.

• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1569-1572
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• 2009

The pharmacokinetics of decursin and decursinol angelate (D/DA) were investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The levels of D/DA and metabolized decursinol in the blood following oral and intravenous administrations declined according to first-order kinetics, with $T_{1/2}$ values of 56.67, 58.01, and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretions of D/DA in bile duct-cannulated rats was $36.10{\pm}2.9%$, $25.35{\pm}3.8%$, and $34.20{\pm}3.2%$, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.161-165
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• 2001

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 $(AUC^0_{\infty})$ of ABT and DAT were significantly increased in mild (p<0.05) and severe FIRRs (p<0.01), but the $AUC^0_{\infty}$ of DAT was more influenced than that of ABT in severe rabbits. There was a good correlation between serum creatinine and both of $AUC^0_{\infty}$ 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.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.973-977
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• 2004

Carvedilol is administered as a racemic mixture of the R(＋)- and S(-)-enantiomers, although they exhibit different pharmacological effects. To investigate the stereoselective pharmacoki-netics, the enantiomeric separation of carvedilol in human plasma was undertaken using capil-lary electrophoresis (CE). Resolution of the enantiomers was achieved using 2-hydoxypropyl-$\beta$-cyclodextrin as the chiral selector. Phosphate buffer (50 mM, pH 4.0) containing 10 mM of 2-hydoxypropropyl-$\beta$-cyclodextrin was used as electrolytic buffer. Achiral separation was carried out with the same electrolytic buffer without chiral selector. Following a single oral administra-tion of 25-mg carvedilol to 11 healthy, male volunteers, stereoselective pharmacokinetic analy-sis was undertaken. The maximum plasma concentrations ( $C_{max}$) were 48.9 and 21.6 ng/mL for (R)-carvedilol and (S)-carvedilol, respectively, determined by the chiral method. The profiles of the plasma concentration of (RS)-carvedilol showed $C_{max}$ of 71.5, 72.2, and 73.5 ng/mL, as determined by the CE, HPLC/FD methods and calculations from the data of the chiral method, respectively.y.y.

• Korean Journal of Clinical Pharmacy
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• v.5 no.2
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• pp.1-12
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• 1995

The purpose of this investigation was to determine pharmacokinetic parameters of gentamicin using linear least square regression(LLSR) and Bayesian analysis in Korean normal volunteers and appendicitis patients. Nonparametric expected maximum(NPEM) algorithm 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 $0.215\pm0.0562,\;0.226\pm0.0325L/kg\;and\;0.339\pm0.0443,\;0.357\pm0.0243hr^{-1}$ for normal volunteers and appendicitis patients using LLSR analysis. Population pharmacokinetic parameters, VS and KS were $0.228\pm0.0614L/kg\;and\;0.00356\pm0.00041(hr{\cdot}mL/min/1.73m^2)^{-1}$ for appendicitis patients using NPEM algorithm. The V and K were $0.232\pm0.0568L/kg\;and\;0.337\pm0.0385hr^{-1}$ for appendicitis patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetics between LLSR and Bayesian analysis.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.200-204
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• 2010

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg) with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life ($t_{1/2}$) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance ($CL_t$). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.

• Korean Journal of Clinical Pharmacy
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• v.14 no.1
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• pp.32-35
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• 2004

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.

• Korean Journal of Clinical Pharmacy
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• v.17 no.1
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• pp.33-37
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• 2007

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of diltiazem (15 mg/kg) after oral administration of diltiazem with or without atorvastatin (0.5, 1.5 and 3.0 mg/kg) in rats. Coadministration of atorvastatin increased significantly (p<0.05, 3.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of diltiazem compared to the control group. The total plasma clearance (CL/F) of diltiazem was decreased significantly (p<0.05, 3.0 mg/kg) compared to the control group. The relative bioavailability (RB%) of diltiazem was increased from 1.14- to 1.49-fold. Coadministration of atorvastatin did not significantly change the elimination rate constant $(K_{el})$, terminal half-life $(T_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of diltiazem. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa.

• Toxicological Research
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• v.18 no.3
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• pp.215-226
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• 2002

Acute or repeated physical exercise affects a large number of physiological parameters including hemodynamics, respiration, pH, temperature, gastrointestinal function and biotransformation, which determine the pharmacokinetics of drugs and chemicals. The rate and the amount of a chemical reaching the active site are altered by physical exercise, which results in significant changes in pharmacolosical/toxicological activity of the chemical. This aspect of physical exercise has vast implication in therapeutics and in safety evaluation, particularly for chemicals that have a low margin of safety. However there appears to be a wide inter- and intraindividual variation in the effects of physical exercise depend-ing on the duration, intensity and type of exercise, and also on the properties of each chemical. It is suggested that more studies need to be done to determine which factor(s) plays a major role in the disposition of chemicals in human/animals performing physical exercise. Certain chemicals induce severe toxicity due to metabolic conversion to reactive intermediate metabolites. it is suggested that repeated exercise may enhance the free radical scavenging system by increasing the activity of antioxidant enzymes. This area of research remain to be explored to elucidate the interaction of exercise and chemical on the antioxidant system.

• The Korean Journal of Nuclear Medicine
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• v.36 no.1
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• pp.8-18
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• 2002

Early and accurate diagnosis of tumors using positron omission tomography (PET) has been the focus of considerable interest due to its high metastasis and mortality rates at late detection. PET radiopharmaceuticals-which exhibit a high tumor-to-background uptake ratio, and appropriate metabolic characteristics, and pharmacokinetics-are attractive tools for tumor imaging. Tumor imaging by these radiopharmaceuticals are based on metabolic and receptor imaging. The former is based on accelerated metabolism in tumor tissue compared to normal tissue and the rate roughly corresponding to the rate of growth of tumors. Radiopharmaceuticals for this purpose include radiolabeled sugars, amino acids, and nucleosides which detect increased glucose utilization, protein synthesis, and DNA synthesis, respectively. Tumor receptor imaging is based on the proliferation of tumor cells regulated by many hormones and growth factors, which bind to the corresponding receptors and exhibit the biological responses Radiopharmaceuticals used to image the tumor receptor systems may be ligands for the specific receptors and antibodies for the growth factor receptors. Some antitumor agents have been labeled with radionuclides and used to study in vivo biodistribution and pharmacokinetics in humans. This overview describes typical PET radiopharmaceuticals used for tumor imaging based on their uptake mechanisms.