• Title/Summary/Keyword: Total body clearance

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Drug Interaction between Flavone and Paclitaxel in Rats (프라본과 파크리탁셀과의 약물상호작용)

  • 최준식;이진환
    • YAKHAK HOEJI
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    • v.47 no.2
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    • pp.98-103
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    • 2003
  • The purpose of this study was to investigate the effect of flavone (20 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (40 mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel in combination with flavone was increased significantly (coadministration p<0.05, pretreatment p<0.0l) compared to that of control. Area under the plasma concentration-time curve (AVC) of paclitaxel with flavone was significantly (coadministration p<0.05, pretreatment p<0.0l) higher than that of control. Peak concentration (Cmax) of paclitaxel with flavone were significantly increased (coadministration p<0.05, pretreatment p<0.01) compared to that of control. Time to peak concentration (Tmax) of paclitaxel with flavone decreased significantly (p<0.05) than that of control. The total body clearance (CLt) and elimination rate constant ($\beta$) of paclitaxel with flavone were significantly reduced (p<0.05) compared to those of control. Half-life (t$_{1}$2/) of paclitaxel with flavone was significantly prolonged (p<0.05) compared to that of control. Based on these results, it might be concluded that flavone may enhance bioavailability of paclitaxel through the inhibition of cytochrome P450 and P-glycoprotein, which are engaged in paclitaxel absorption and metabolism in liver and gastrogintestinal mucosa, respectively.

Physiological Pharmacokinetic Model of Ceftriaxone Disposition in the Rat and the Effect of Caffeine on the Model

  • Kwon, Kwang-Il;Bourne, David-W.A.
    • Archives of Pharmacal Research
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    • v.13 no.3
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    • pp.227-232
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    • 1990
  • A Physiologically based pharmacokinetic model was used to describe the distribition and elimination of cefriazone in the rat. To validate the practical application of the model, the effect of cffeine on the model was also examined. The model consisted of eleven compartments representing the major sites for ceftriaxone distribution including carcass which served as a residual compartment. Elimination was represented by renal and hepatic (metabolic biliary )excretion with GI secretion and re-absorption. The drug concentrations in most of the tissues were simulated using flow limited equations while brain levels were simulated using membrane limited passive diffusion distribution. The experimental data were obtained by averaging the concentration of drug in the plasma and tissues of five rats after i. v. injection of cefriazone 100 mg/kg without and with caffeine 20 mg/kg. The data for the amount of ceftriazone excreted in urine and gut contents were used to apportion total body clearance. HPLC with UV detection was used for the assay with 0.1-0.2 $\mu$g/ml sensitivity. The great majority of drug concentrations with and without caffeine show reasonably good agreements to the simulation results within 20%. The effect of caffeine on renal and hepatic clearances was apparent with 18.8% and 18.6% increase in the model values, respectively.

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Pharmacokinetics of eupatilin, an active componets of Stillen\ulcorner, a new antigastritic agent,in rats

  • Jang, Ji-Myun;Park, Kyung-Jin;Kim, Dong-Goo;Shim, Hyun-Joo;Ahn, Byung-Ok;Kim, Soon-Hoe;Kim, Won-Bae
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.243.1-243.1
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    • 2003
  • The pharmacokinetics of eupatilin (an active components of Stillen, a new antigastritic agent) were investigated using UV-HPLC method. The quantitation limit of eupatilin was 10 ng/ml in plasma. After intravenous administration of eupatiln, 30 mg/kg to rats, the plasma concentrations of unchanged eupatilin declined rapidly with the mean terminal half-life of 0.101 hr. Total body clearance was 121 ml/min/kg, and fractions of dose excreted in urine and feces for 24 hr were only 2.5% and 0.919%, respectively. (omitted)

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A Simple Dosing Scheme for Intravenous Busulfan Based on Retrospective Population Pharmacokinetic Analysis in Korean Patients

  • Choe, Sang-Min;Kim, Gayeong;Lim, Hyeong-Seok;Cho, Sang-Heon;Ghim, Jong-Lyul;Jung, Jin-Ah;Kim, Un-Jib;Noh, Gyu-Jeong;Bae, Kyun-Seop;Lee, Dong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.273-279
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    • 2012
  • Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

Effects of Supplemental Recombinant Bovine Somatotropin (rbST) and Cooling with Misters and Fans on Renal Function in Relation to Regulation of Body Fluids in Different Stages of Lactation in Crossbred Holstein Cattle

  • Boonsanit, D.;Chanpongsang, S.;Chaiyabutr, N.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.3
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    • pp.355-365
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    • 2010
  • The aim of this study was to investigate the effect of supplemental recombinant bovine somatotropin (rbST) and cooling with misters and fans on renal function in relation to regulation of body fluids in different stages of lactation in crossbred Holstein cattle. Ten, 87.5% crossbred Holstein cattle were divided into two groups of 5 animals each, housing in a normal shaded barn (NS) and in a shaded barn with a mister-fans cooling system (MF). The experiment in each group was divided into 3 phases, early- (Day 75 postpartum), mid- (Day 135 postpartum), and late stage of lactation (Day 195 postpartum). The pre-treatment study was conducted on the starting day of each stage of lactation and the treatment study was performed after the end of the pre-treatment, during which the animal was injected with 500 mg of rbST (POSILAC) every 14 days for three times. During the study, ambient temperature at the hottest period daily in the MF barn was significantly lower, while relative humidity was higher than that of the NS barn. The temperature humidity index (THI) in both barns ranged from 79-85 throughout the periods of study. Cows in the MF barn showed a lower rectal temperature and respiration rate as compared with cows in the NS barn. The effect of rbST administration increased both rectal temperature and respiration rates of cows housed in either the NS or MF barn. Milk yield significantly increased in cows treated with rbST in all stages of lactation. Increases in mammary blood flow, accompanied by increases of total body water (TBW), extracellular fluid (ECF), blood volume (BV) and plasma volume (PV), were observed in both groups of cows receiving rbST in all stages of lactation. No alterations of renal blood flow and glomerular filtration rate were observed in cows receiving rbST, but decreases in urinary excretion and fractional excretion of sodium, potassium and chloride ions appeared to correlate with reduction in the rate of urine flow and osmolar clearance during rbST administration. These results suggest that the effect of rbST supplementation to cows housed either in NS or MF barns on body fluid volume expansion is attributable to changes in the rate of electrolyte excretion by the kidney. The increased availability of renal tubular reabsorption of sodium, potassium and chloride ions during rbST treatment was a major factor in retaining body water through its colligative properties in exerting formation of an osmotic force mechanism.

Pharmacokinetics of Astromicin Following a Single Intravenous Infusion in Healthy Korean Subjects (정상성인 한국인에서 아스트로마이신 1회 점적 주사후 약물동태학적 평가)

  • Bok, Hae Sook;Choi, Kyung Eob;Kim, Yeon Hwa;Peck, Kyong Ran;Song, Jae Hoon
    • 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.

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Predictive Factors Affected to Forced Vital Capacity in Children with Cerebral Palsy (뇌성마비 아동에서 노력성 폐활량에 영향을 미치는 요인 분석에 관한 연구)

  • Nam, Ki Seok;Lee, Hye Young
    • The Journal of Korean Physical Therapy
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    • v.25 no.4
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    • pp.204-209
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    • 2013
  • Purpose: Children with cerebral palsy generally have a high incidence of respiratory problem, resulted from poor coughing, airway clearance problem, respiratory muscle weakness, kyphoscoliosis and so forth. The purpose of this study is to investigate the possible factors that can be affected to forced vital capacity (FVC) in children with cerebral palsy. Methods: Total thirty six children with diplegic and hemiplegic cerebral palsy were recruited in this study. They were evaluated by general demographic data (i.e., age, gender, body mass index (BMI)) and variables related to respiratory functions (i.e., chest mobility, waist mobility, maximal phonation time, and maximum inspiratory/expiratory pressure (MIP/MEP)). The correlation between forced vital capacity and the rested variables were analyzed, and multiple regression with stepwise method was conducted to predict respiratory function, in terms of FVC as the dependent variable, and demographic and other respiratory variables as the independent variable. Results: FVC showed a significant correlation with waist mobility (r=0.59, p<0.01), maximal phonation time (r=0.48, p<0.05), MIP (r=0.73, p<0.01), and MEP (r=0.60, p<0.01). In addition, the multiple regression analysis model indicated that FVC could be predicted by the assessment of each waist mobility and MIP. Conclusion: These finding suggest that respiratory function is related to body size and respiratory muscle strength, and that BMI, waist mobility, and MIP can be predictable factors to affected respiratory function in term of FVC.

Bioavailability of Ranitidine Tablets in Rats (흰쥐에서 라니티딘제제의 생체이용률)

  • 이미숙;구영순
    • YAKHAK HOEJI
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    • v.39 no.6
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    • pp.636-644
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    • 1995
  • Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.

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A Case Report of a Cerebral Infarction Patient whose Diabetic Nephropathy Improved with Serum Creatinine Level by Oryeong-san and Acupuncture Therapy (오령산 투여 및 침치료 후 당뇨병성 신증의 혈청 크레아티닌 수치가 호전된 뇌경색 환자 증례보고)

  • Hong, Seung-Cheol;Park, Song-Won;Yi, Chansol;Noh, Hyeonseok;Ha, You-Kyung;Choi, Dong-Jun
    • The Journal of the Society of Stroke on Korean Medicine
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    • v.18 no.1
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    • pp.13-22
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    • 2017
  • ■ Objectives This case is to report the effect of Oryeong-san and acupuncture therapy on serum creatinine level of a cerebral infarction patient with diabetic nephropathy. ■ Methods A female Korean patient was treated with Oryeong-san, acupuncture for total 32 days. We observed renal function test, input/output balance, body weight, hand and foot circumferences, and other symptoms like edema, urination, and any adverse event. ■ Results After treatment, serum creatinine level was improved to 2.48mg/dL from 3.45mg/dL at admission, and foot circumference was decreased to 18.5~18.9cm from 22.0~22.5cm without any adverse event. However, we couldn't find any significant differences on input/output balance, body weight, or symptoms of urination. ■ Conclusion This case suggests that Oryeong-san and acupuncture therapy could be effective in improving serum creatinine clearance of cerebral infarction patient with diabetic nephropathy.

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Effects of the Fermented Extract Using the Leaves of Pinus densiflora on Hyperlipidemia Rats (솔잎 발효액이 백서의 고지혈증 미치는 영향)

  • Kang Dae Gill;Lee Yun Mi;Oh Hyun Cheol;Mun Yeun Ja;Lee Ho Sub;Woo Won Hong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.140-145
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    • 2003
  • The present study was designed to examine whether the fermented extract using the leaves of Pinus densiflora (FPD), has an ameliorative effect on the lipid metabolism in rats with hyperlipidemia. The body weight gain was attenuated by the adminstration of either 1-dose (2 ml/kg/day) or 2-dose (4 ml/kg/day) of FPD for 2 weeks compared with that of control or hyperlipidemia rats, while blood glucose, systolic blood pressure, sGOT, and sGPT were not altered. Serum total cholesterol, LDL-cholesterol, and athelosclerotic index were partially restored by the administration of 2-dose of FPD in rats with hyperlipidemia without changes of serum HDL-cholesterol, total lipid, and triglyceride concentration. The FPD also partially ameliorated renal functional parameters including plasma cleatinine and creatinine clearance which were attenuated in rats with hyperlipidemia. These results suggest that FPD has an ameliorative effect on the lipid metabolism and renal function in rats with hyperlipidemia.