• Title/Summary/Keyword: WinNonlin

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Antimicrobial Activity of Florfenicol Against Fish Pathogenic Bacteria and Pharmacokinetics in Blood of Cultured Olive Flounder by Oral Administration (Florfenicol의 어류 병원성 세균에 대한 항균 효과와 경구 투여후 넙치 혈액에서의 약물동태학적 특성)

  • Jung, Sung-Hee;Seo, Jung-Soo
    • Journal of Fisheries and Marine Sciences Education
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    • v.25 no.5
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    • pp.1079-1087
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    • 2013
  • The pharmacokinetics of florfenicol (FF) after oral administration was studied in the cultured olive flounder, Paralichthys olivaceus, using high performance liquid chromatography (HPLC). After single administration of FF (20 mg/kg body weight) by oral route in olive flounder ($700{\pm}50$ g, $23{\pm}1.5^{\circ}C$), the concentration in the serum was determined at 1, 5, 10, 15, 24, 30, 50 and 168 h post-dose. The kinetic profile of absorption, distribution and elimination of FF in serum were analyzed fitting to a two-compartment model by WinNonlin program. The area under the concentration-time curve (AUC), maximum concentration ($C_{max}$), time for maximum concentration ($T_{max}$) and elimination time were 22.51 ${\mu}g{\cdot}h/mL$, 0.84 ${\mu}g/mL$, 8.62 h and 447 h, respectively. The results of this study related to dosage and withdrawal times could be used for prescription of FF in field for the treatment of bacterial diseases in olive flounder.

Comparative Bioavailability and Metabolism of Two Capsule Formulations of Fluoxetine in Human Volunteers (플루옥세틴 캅셀제의 지원자에 대한 생체이용율 및 대사율 비교)

  • Kang, Won-Ku;Park, Yong-Soon;Cho, Gyu-Haeng;Choi, Jun-Sik;Kwon, Kwang-Il
    • YAKHAK HOEJI
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    • v.42 no.5
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    • pp.513-518
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    • 1998
  • Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

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Pharmacokinetics of oxytetracycline in olive flounder (Paralichthys olivaceus) by intramuscular injection (Oxytetracycline을 근육 주사한 넙치 (Paralichthys olivaceus)의 약물동태학적 특성)

  • Jung, Sung-Hee;Choi, Dong-Lim;Kim, Jin-Woo;Jo, Mi-Ra;Seo, Jung-Soo;Ji, Bo-Young
    • Journal of fish pathology
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    • v.22 no.1
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    • pp.91-95
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    • 2009
  • The pharmacokinetic properties of oxytetracycline (OTC) were studied after intramuscular injection to cultured olive flounder, Paralichthys olivaceus. Plasma concentrations of OTC were determined after dosage of 12.5, 25 and 50 ㎎/㎏ body weight in olive flounder (average 600 g, $23{\pm}1{^{\circ}C}$). Plasma samples were taken at 3, 5, 10, 15, 24, 32, 48, 72, 120, 168, 240 and 360 h post-dose. With 25 and 50 ㎎/㎏, the peak plasma concentrations of OTC, which attained at 5 h post-dose, were 0.99 and 1.49 $\mu{g}/m\ell$, respectively. However, the peak plasma concentration of 12.5 ㎎/㎏ was 0.35 $\mu{g}/m\ell$ after 10 h post-dose. Plasma concentrations of OTC were not measurable at 360 h post-dose in all doses. The kinetic profile of absorption, distribution and elimination of OTC in plasma were analyzed fitting to a 1-compartment model by Win-Nonlin program. The following parameters were calculated for 12.5, 25 and 50 ㎎/㎏ body weight, respectively: AUC (the area under the concentration-time curve)?D���D24.98, 44.67 and 50.45 $\mu{g}$ $h/m\ell$ $T_{1/2}$ (half-life) ?D���D0.42, 0.59 and 0.41 h; $T_{max}$ (time for maximum concentration)?D���D8.46, 6.34 and 2.66 h; $C_{max}$ (maximum concentration)?D���D0.30, 0.63 and 1.13 $\mu{g}/m\ell$.

Effects of temperature on pharmacokinetics of oxolinic acid in black rockfish, Sebastes schlegeli following oral administration (조피볼락, Sebastes schlegeli에 경구투여된 oxolinic acid의 약물동태에 미치는 수온의 영향)

  • Jung, Sung-Hee;Kim, Jin-Woo;Seo, Jung-Soo;Jee, Bo-Young;Park, Myoung-Ae
    • Journal of fish pathology
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    • v.23 no.2
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    • pp.221-227
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    • 2010
  • Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of oxolinic acid (OA) were studied after oral administration to cultured black rockfish, Sebastes schlegeli. Serum concentrations of OA were determined using HPLC-UV detector after a single dosage of 60 mg/kg body weight (average about 500 g). The peak serum concentrations of OA at $23{\pm}1.5^{\circ}C$ and $13{\pm}1.5^{\circ}C$ were $0.60{\mu}/ml$ at 30 h and $2.22{\mu}g/ml$ at 10 h post-dose, respectively. Better absorption of OA was noted at $13{\pm}1.5^{\circ}C$ compared to $23{\pm}1.5^{\circ}C$. The elimination of OA from serum was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. Both absorption and elimination of OA were affected significantly by temperature. The kinetic profile of absorption, distribution and elimination of OA in serum was analyzed by fitting to a two compartment model, with WinNonlin program. The AUC, Tmax and Cmax at $23{\pm}1.5^{\circ}C$ were $42.16{\mu}g{\cdot}h/m\ell$, 26.13 h and $0.43{\mu}g/ml$, respectively. The AUC, Tmax and Cmax at $13{\pm}1.5^{\circ}C$ were $131.98{\mu}g{\cdot}h/ml$, 8.81 h and $2.04{\mu}g/ml$, respectively.

The Experimental Studies on Antithrombotic Effects of Hyunhosaiksan (현호색산의 항혈전작용에 대한 연구)

  • Lim Min Cheul;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.4
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    • pp.930-938
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    • 2003
  • The purpose of the present study was to investigate the effects of Hyunhosaiksan (HHS) on antithrombotic actions which include blood activation, thrombus removal, warming of circulating blood, and the control of pain on abdomen and lower and upper burning spaces. HHS significantly inhibited platelet aggregation induced by ADP and epinephrine in a HHS dose-dependent manner when analyzed by the Sigmoid Emax model in WinNonlin. EC50 values of HHS were 1.71 ㎍/ml and 0.004 ㎍/ml for ADP and epinephrine respectively. In the vivo study, HHS inhibited pulmonary embolism induced by collagen and epinephrine, which was however statistically insignificant. HHS increased number of platelets, APTT and volume of fibrinogen significantly as compared with the control group in dextran-induced thrombus model. Furthermore, HHS stimulated levels of blood flow in vivo though its effect was not observed in vitro. These results suggest that Hyunhosaiksan (HHS) can be used for treating numerous diseases related with blood aggregation and circulation problems. Further systematic investigations on the synergic effects among drugs used in the oriental medicine as well as in the western medicine in relation to thrombosis therapy would provide an important insight into the potential therapeutic applications.

The Pharmacokinetics of Erythromycin in Cultured Paralichthys olivaceus after Oral administration (경구투여에 의한 양식산 넙치내 Erythromycin의 약물동태학적 특성 분석)

  • Seo, Jung-Soo;Jeon, Eun-Ji;Jung, Sung-Hee;Park, Myung-Ae;Kim, Na-Young
    • Journal of Fisheries and Marine Sciences Education
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    • v.26 no.2
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    • pp.316-321
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    • 2014
  • The pharmacokinetics of erythromycin (EM) after oral administration was studied in the cultured olive flounder, Paralichthys olivaceus, using LC/MS/MS. After single- or multiple-dose administration of EM (50, 100, 200 mg/kg body weight and 50 mg/kg for 5 days) by oral route in olive flounder ($350{\pm}40g$, $22{\pm}0.5^{\circ}C$), the concentration in the serum was determined at 1, 3, 6, 9, 24, 72, 120, 168, 264, 360, 504 and 720 h post-dose. The kinetic profile of absorption, distribution and elimination of EM in serum were analyzed fitting to a two-compartment model by WinNonlin program. The area under the concentration-time curve (AUC), maximum concentration ($C_{max}$), time for maximum concentration ($T_{max}$) following oral administration of 50, 100 and 200 mg/kg b.w. and 50 mg for 5 days. EM was $165.3hr^*{\mu}g/m{\ell}$ ($C_{max}$, $34.63{\mu}g/m{\ell}$; $T_{max}$, 1.56 hr), $212.8hr^*{\mu}g/m{\ell}$ ($C_{max}$, $60.38{\mu}g/m{\ell}$; $T_{max}$, 3.99 hr), and $592.37hr^*{\mu}g/m{\ell}$ ($C_{max}$, $63.01{\mu}g/m{\ell}$; $T_{max}$, 4 hr), respectively. The results of this study related to dosage and ${\mu}{\cdot}$withdrawal times could be used for prescription of EM in field for the treatment of bacterial diseases in olive flounder.

Validation of a HPLC Method for Determination of Pentoxifylline in Human Serum and Its Application to Single-dose Pharmacokinetics (인체혈청 중 펜톡시필린의 정량을 위한 HPLC 분석법의 점증 및 단일용량 투여에 의한 약물동태)

  • Sung, Min Kyung;Park, Hyo Min;Kim, Na Hyung;Chung, Soo Yeon;Go, Eun Jung;Lee, Hwa Jeong
    • Korean Journal of Clinical Pharmacy
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    • v.15 no.1
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    • pp.46-49
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    • 2005
  • A simple HPLC method was employed for the determination of pentoxifylline in human serum. After addition of internal standard (IS, 50 uL of 3 ug/mL chloramphenicol methanol solution) into the serum sample, the drug and IS were extracted by dichloromethane. Following a 1-min vortex-mixing and a 15-min centrifugation at 3500 게m, the organic phase was transferred and evaporated to dryness under a vacuum. The residue was reconstituted with 120 ${\mu}L$ of mobile phase and 50 ${\mu}L$ was injected into C18 column with a mobile phase composed of 0.034 M phosphoric acid adjusted to pH 4 with 10 M NaOH and acetonitrile (75:25, v/v). The samples were detected using an ultraviolet detector at 273 nm. The method was simple, specific and validated with a limit of 10 ng/mL. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of this method was evaluated by analysis of human serum after oral administration of a single 400 mg dose to 8 healthy subjects. The pharmacokinetic parameters for pentoxifylline in human subjects were calculated using WinNonlin program. As a result, $AUC_{t},\;C_{max},\;T_{max}$ and $t_{1/2}$ were $962.28{\pm}645.69\;ng{\cdot}/mL$, $132.82{\pm}42.05$ ng/mL, $2.06{\pm}2.68$ hr and $8.74{\pm}4.38$ hr, respectively. Based on the results, this validated method appears to be useful fur the pharmnacokinetic study of pentoxifylline in humans.

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Pharmacokinetic Study of Promethazine in Korean Healthy Subjects Using a Validated HPLC Method

  • Jang, Jung-Ok;Go, Eun-Jung;Kim, Na-Hyung;Chung, Soo-Yeon;Park, Hyo-Min;Lee, Hwa-Jeong
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.118-122
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    • 2005
  • The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and the analyte was quantified with UV detection at 251 nm. The calibration curve of the drug was linear over the range of 1-40ng/mL in human serum and the limit of quantification (LOQ) was 1 ng/mL. This analytical method was validated and shown to be specific, accurate, precise and reproducible. This method was applied to pharmacokinetic study of promethazine in Korean healthy volunteers following an oral administration of two 25 mg Himazin tablets (50 mg promethazine ${\cdot}$HCI) after overnight fasting. Serum samples were collected at given intervals over a 36-hour period (12 points) and pharmacokinetic parameters were determined from serum concentration-time profile using WinNonlin program. The estimated $AUC_{0__\infty}$, $AUC_{0_\infty}$, $C_{max}$, $T_{max}$ and $t_{1/2}$ of promethazine obtained from Korean healthy subjects were 103.84 ${\pm}$84.30 ng${\cdot}$hr/mL, 87.94${\pm}$81.02 ng${\cdot}$hr/mL, 13.43${\pm}$10.92 ng/mL, 2.00${\pm}$1.16 hr and 5.88${\pm}$3.47 hr, respectively.

Plasma pharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women

  • Chang, Youngeun;Choue, Ryowon
    • 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.

Bioequivalence and Pharmacokinetic study of Gabapentin 300mg Capsules using Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS) in Volunteers (LC/MS/MS를 이용한 가바펜틴 300 mg 캡슐의 성인 지원자에 대한 생물학적 동등성 및 약물동태 연구)

  • Jeong, Ji-Hoon;Kwon, Jun-Tack;Yun, Hwi-Yeol;Kang, Won-Ku;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.16 no.1
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    • pp.63-68
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    • 2006
  • Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is anew antiepileptic drug related to ${\gamma}-aminobutyric$ acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced $2{\times}2$ crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. $WinNonlin^{(R)}$, the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by $1/(predieted\;y)^2$ was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters $(AUC_{0-24hr},\;AUC_{inf},\;C_{max}\;and\;T_{max})$ and other parameters $(K_a,\;K_{el},\;V_d/F\;and\;Cl/F)$ of $Gapentin^{TM}$ (test drug) and $Neurontin^{TM}$ (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed $AUC_{0-24hr}\;and\;C_{max}$ were $log(0.9106){\sim}log(1.l254)\;and\;log(0.8521){\sim}log(1.0505)$, respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.

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