• Archives of Pharmacal Research
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• 제26권9호
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• pp.763-767
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• 2003

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm $\times$ 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mm$\times$4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time ($T_{1/2(\alpha)}$) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time ($T_{1/2(\beta)}$) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.

• 대한수의학회지
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• 제43권2호
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• pp.203-210
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• 2003

The purpose of this study is to investigate the pharmacokinetics and tissue distribution of recombinant bovine somatotropin (rBST) after subcutaneous adminstration of $^{125}I-rBST$ in male and female rats. A solid state conjugation (Iodo-bead$^{(R)}$) method was confirmed useful for producing $^{125}I-rBST$ because the administration of the conjugated form enabled enough to determine time- concentration relationships of rBST in rats. Subcuatenous administrations showed sex differences that female ($t_{1/2,kc}$, 2.87 h) revealed rapid elimination as compared to male ($t_{1/2,ke}$, 4.81 h), with the absorption ($t_{1/2,ka}$ in male being 0.3 h and that in female 0.75 h) in the reverse order. For subcutaneous administration of rBST in male rats, the liver was the highest in amount, followed by kidney, testes, muscle, and stomach, at the slaughtering tame of 1, 6, 12 and 24 h. But the testes was the highest at the 48 h slaughtered animals, followed by liver, kidney, stomach, and muscle. In slaughtered females at 1, 6, and 12 h after the administration of rBST, the liver was the highest, followed by ovary, kidney, small intestine, and stomach. At 24 and 48 h slaughtered female rats, the ovary was the highest, the liver the second, and the kidney the third.

• Clinical and Experimental Pediatrics
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• 제60권2호
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• pp.50-54
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• 2017

Purpose: The aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM. Methods: A retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day. Results: Seventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was $8.7{\mu}g/mL$. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults. Conclusion: LEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.

• Investigative Magnetic Resonance Imaging
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• 제17권4호
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• pp.259-266
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• 2013

목적: DTPA-bis-amide (L3) Gd(III) 복합체의 약동학 및 생체내 분포특성을 조사하고자 하였다. 대상과 방법: Sprague-Dawley 쥐의 꼬리정맥을 통하여 0.1 mmol Gd/kg의 DTPA-bis-amide (L3) Gd(III) 복합체를 주사한 후 약동학 및 생체내 분포 특성을 조사하였다. 조직 및 장기 그리고 혈중 Gd 농도를 ICP-AES를 사용하여 정량 측정하였으며 혈중 약동학적 파라미터는 two-compartment 모델을 사용하여 계산하였다. 결과: DTPA-bis-amide (L3) Gd(III) 복합체의 혈중 반감기는 ${\alpha}$-phase의 경우 $2.286{\pm}0.11$ min 그리고 ${\beta}$-phase의 경우 $146.1{\pm}7.5$ min 이었다. 생체내 분포특성은 주요 배설 경로는 신장을 통한 배설이 주요 경로였으며 일부 담도계를 통한 배설이 확인되었다. 또한 Gd(III)의 농도비는 다른 장기에 비해 간과 비장에서 매우 높은 농도를 보였으며 일부 Gd(III)이 정맥주사 후 7일후에 혈액 및 일부 장기에서 매우 소량 검출되었다. 결론: 새로운 조영제인 DTPA-bis-amide (L3) Gd(III) 복합체는 혈중 잔류시간이 상대적으로 길면서도 체내 축적없이 체외로 배출되는 특성을 나타내었다. 따라서 친지질성과 친수성의 균형이 잘 이루어진 가돌리늄 조영제의 합성은 향후 blood pool MRI 조영제로써의 가능성이 매우 높은 것으로 판단된다.

• Archives of Pharmacal Research
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• 제12권3호
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• pp.154-159
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• 1989

Pharmacokinetics and urinary excretion of sulfamethoxazole were investigated in healthy sheep. From the plasma disappearance curves after intravenous bolus injection (50 mg/kg), the half-life and volume of distribution were found to be 76 $\PM$14 min and 0.41 $\PM$ 0.18 lit/kg respectively. Body clearance was 4.06 $\PM$ 1.03 ml/kg/min. Very low Concentration of ddrug was present in plasma after 3 hours of administration and plasma level at 6 hour was only 4.4 $\PM$ 2.0 $\mu$g/ml. The renal clearance of sulfamethoxazole (22 $\PM$ 2.17 ml/min/10 kg) exeeded the creatinine clearance (9.78 $\PM$ 1, 57 ml/min/ 10 kg) which may be due to involvement of active tubular secretion and pH dependent back diffusion. Half of the dose of sulfamethoxazole was excreted as unchanged free drug while acetylated amine comprised of 20 percent within the first 6 hours of drug administration.

• 약학회지
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• 제40권1호
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• pp.1-9
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• 1996

The purpose of this investigation was to determine pharmacokinetic parameters of gentamicin using nonlinear least square regression(NLSR) and Bayesian analysis in Korean normal volunteers and gastrointestinal surgical patients. Nonparametric expected maximum(NPEM) method 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 $0.226{\pm}0.032,\;0.231{\pm}0.063L/Kg\;and\;0.357{\pm}0.024,\;0.337{\pm}0.041hr^{-1}$ for normal volunteers and gastrointestinal surgical patients using NLSR analysis. Population pharmacokinetic parameters, KS and VS were $0.00344{\pm}0.00049(hr{\cdot}ml/min/1.73m^2)^{-1}\;and\;0.214{\pm}0.0502L/Kg$ for gastrointestinal surgical patients using NPEM method. The V and K were $0.216{\pm}0.048L/Kg\;and\;0.336{\pm}0.043hr^{-1}$ for gastrointestinal surgical patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetics between NLSR and Bayesian analysis in gastrointestinal surgical patient.

• 약학회지
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• 제42권2호
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• pp.181-186
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• 1998

This study was attempted to investigate the pharmacokinetics of cyclosporine (10mg/kg, oral) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. The area under the curve (AUC) of blood cyclosporine concentration versus time was significantly increased ($CCI_4$-induced hepatic disorder. Elimination rate constant (Kel) was significantly decreased (p<0.05, p<0.01) in rabbits with $CCI_4$ 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 $CCI_4$-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.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.397-415
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• 2002

This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide 2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance level should be based on data on the relative affinities of interacting substrates for the transport systems involved along with knowledge on the pharmacokinetics of these agents as well as the chosen dose regimen in the studied species. This review highlights the importance of multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic compounds of various charge, implying potential transport interactions that can affect body distribution and organ clearance.

• Journal of Ginseng Research
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• 제46권2호
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• pp.206-213
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• 2022

Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.

• Journal of Ginseng Research
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• 제42권1호
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• pp.27-34
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• 2018

Background: The use of different methods for the processing of ginseng can result in alterations in its medicinal properties and efficacy. White ginseng (WG), frozen ginseng (FG), and red ginseng (RG) are produced using different methods. WG, FG, and RG possess different pharmacological properties. Methods: WG, FG, and RG extracts and pure ginsenosides were administered to rats to study the pharmacokinetics and tissue distribution characteristics of the following ginsenosides-DRg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the plasma and tissues were determined using UPLC-MS/MS. Results: The rate and extent of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different methods used in processing the ginseng samples. The areas under the plasma drug concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re, Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and Rb1 were significantly (p < 0.05) higher in the tissues than those of the pure ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were significantly higher than those from the WG and FG extracts in the heart, lungs, and kidneys of the rats. Conclusion: Our results show that the use of different methods to process ginseng might affect the pharmacokinetics and oral bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd, and Rb1.