• Korean Journal of Clinical Pharmacy
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• v.13 no.2
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• pp.55-58
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• 2003

Astromicin is an aminoglycoside antiviotic that is structually different from conventional aminoglycosides. Astromicin has been shown to be active against aerobic Gram-negative bacilli. The pharmacokinetics of astromicin were determined in 12 healthy volunteers ($65.5\pm5.23\;kg$ of body weight) following a 30-min continuous intravenous infusion at a dose of 200 mg. The plasma and urine samples were collected up to 24 h and drug concentrations were measured by a bioassay using Bacillus subtilis. Pharmacokinetic parameters were calculated by fitting individual concentration-time curve to a one-exponential decay model. The plasma levels were $16.9\pm1.68\;and\;1.05\pm0.346\l{\mu}g/ml$ at 0 h and 8 h after the infusion, respectively. The elimination half-life of astromicin was $1.86\pm0.360\;h$ The volume of distribution was $0.182\pm0.0164\;L/kg$, and the total body clearance was $5.25\pm1.74\;L/h$. These pharmacokinetic parameters were similar to these of gentamicin, tobramycin, and amikacin. Therefore, it is recommended that therapeutic drug monitoring of astromicin could be conducted in a similar fashion as the other aminoglycosides.

• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.258-266
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• 2017

Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and to elucidate individual characteristics to affects alcohol's PK or PD including dissolved oxygen. Methods: Following multiple intakes of total 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser (Lion SD-400 $Alcolmeter^{(R)}$). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteen healthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-order absorption and Michaelis-Menten elimination kinetics. $K_a$, V/F, $V_{max}$, $K_m$ is $8.1hr^{-1}$, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced $V_{max}$ (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model of temporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory $E_{max}$ model. $K_{e0}$, $I_{max}$, $E_0$, $IC_{50}$ were $0.23hr^{-1}$, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested that this PK/PD model was robust and has good precision.

• Biomolecules & Therapeutics
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• v.11 no.3
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.364-370
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• 2011

The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${\mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.107-111
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• 2007

Epigallocatechin gallate (EGCC), a flavonoid, is the main component of green tea extracts. EGCG has been reported to be an inhibitor of P-glycoprotein (P-gp) and cytochrom P450 3A(CYP3A4). This study investigated the effect of long-term administration of EGCG on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats pretreated with EGCG (7.5 mg/hg) for 3 and 9 days. Compared to oral control group, the presence of EGCG significantly (p<0.01) increased the area under the plasma concentration-time curve (AUC) of verapamil by 102% (coad), 83.2% (3 days) and 52.3% (9 days), and the peak concentration $(C_{max})$ by 134% (coad), 120% (3 days) and 66.1% (9 days). The absolute bioavailability (A.B.%) of verapamil was significantly (p<0.01) higher by 8.4% (coad), 7.7% (3 days), 6.4% (9 days) compared to control (4.2%), and presence of EGCG was no significant change in the terminal half-life $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of verapamil. Our results indicate that EGCG significantly enhanced oral bioavailability of verapamil in rats, implying that presence of EGCG could be effective to inhibit the CYP3A4-mediated metabolism and P-gp efflux of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with EGCG or EGCG-containing dietary.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.397-402
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• 2005

The purpose of this study was to investigate the effect of probencid on the pharmacokinetics of oral pranoprofen in rats. Pranoprofen (5 mg/kg) was coadministered with 5, 10 or 20 mg/kg of probenecid orally. Coadministration of probenecid significantly altered the pharmacokinetics of pranoprofen at 10 and 20 mg/kg. Compared with the control group, probenecid significantly (p<0.05) increased the absorption rate constant $(K_{a})$, the peak concentrations $(C_{max})$ and accordingly the area under the plasma concentration-time curve (AUC) of pranoprofen at the dose level of 10 mg/kg and 20 mg/kg of probenecid. The relative bioavailability (RB%) of pranoprofen was 1.64- to 1.82- fold increased. Furthermore, 10 and 20 mg/kg probenecid induced the decreased elimination constants $(K_{el})$ and the prolonged half-lives $(t_{1/2})$ of pranoprofen with significance (p<0.05). Coadministration of 10 and 20 mg/kg of probenecid lowered the excreted amounts of pranoprofen in the urine by 21.3-22.5% compared to the control. Overall, probenecid enhanced the bioavailability of pranoprofen and decreased its elimination rate to a greater degree at higher dose. Based on the effect of probenecid on the pharmacokinetic behavior of pranoprofen, the dosage regimen of pranoprofen should be taken into consideration when pranoprofen is administered with probenecid in the clinical setting to the patients especially with peptic ulcer or renal failure.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.249-253
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• 2012

We analyzed the pharmacokinetics of C3G on data from twelve subjects, after 2-week multiple dosing of black bean (Phaseolus vulgaris, Cheongjakong-3-ho) seed coat extract, using the mixed effect analysis method (NONMEM, Ver. 6.2), as well as the conventional non-compartmental method. We also examined the safety and tolerability. The PK analysis used plasma concentrations of the C3G on day 1 and 14. There was no observed accumulation of C3G after 2-week multiple dosing of black bean seed coat extract. The typical point estimates of PK were CL (clearance)=3,420 l/h, V (volume)=7,280 L, Ka (absorption constant)=9.94 $h^{-1}$, ALAG (lag time)=0.217 h. The black bean seed coat extract was well tolerated and there were no serious adverse events. In this study, we confirmed that a significant amount of C3G was absorbed in human after given the black bean seed coat extract.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.107-115
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• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

• Nutrition Research and Practice
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• v.7 no.5
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• pp.393-399
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• 2013

Asian populations are thought to receive significant health benefits from traditional diets rich in soybeans due to high isoflavone contents. However, available epidemiologic data only weakly support this hypothesis. The present study was carried out to assess the pharmacokinetics of isoflavones in South Korean women after ingestion of soy-based foods. Twenty-six healthy female volunteers (20-30 y old) consumed three different soy products (i.e., isogen, soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma and urine isoflavone concentrations were measured by high-performance liquid chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic parameters were determined using the WinNonlin program. The area under the curve (AUC) for plasma daidzein levels of the soymilk group ($2,101{\pm}352ng{\cdot}h/mL$) was significantly smaller than those of the isogen ($2,628{\pm}573ng{\cdot}h/mL$) and fermented soybean ($2,593{\pm}465ng{\cdot}h/mL$) groups. The maximum plasma concentration ($C_{max}$) of daidzein for the soymilk group ($231{\pm}44$ ng/mL) was significantly higher than those of the isogen ($160{\pm}32$ ng/mL) and fermented soybean ($195{\pm}35$ ng/mL) groups. The half-lives of daidzein and genistein in the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented soybean group, and 33% and 22% for the soymilk group. In conclusion, our data indicated that soy products containing high levels of isoflavone aglycone are more effective for maintaining plasma isoflavone concentrations. Additional dose-response, durational, and interventional studies are required to evaluate the ability of soy-based foods to increase the bioavailability of isoflavones that positively affect human health.

• 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.