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ABSTRACT: It was reported that in rats with water deprivation for 72 h with food (dehydration rat model), the expression of CYP2E1 was 3-fold induced with an increase in mRNA level and glucose supplementation instead of food during 72-h water deprivation (dehydration rat model with glucose supplementation) inhibited the CYP2E1 induction in dehydration rat model. It was also reported that chlorzoxazone (CZX) is metabolized to 6-hydroxychlorzoxazone (OH-CZX) mainly via CYP2E1 in rats. Hence, the effects of glucose supplementation on the pharmacokinetics of CZX and OH-CZX were investigated after intravenous administration of CZX at a dose of 25 mg/kg to control male Sprague-Dawley rats and dehydration rat model and dehydration rat model with glucose supplementation. Based on the above mentioned results of CYP2E1, it could be expected that increased formation of OH-CZX in dehydration rat model could decrease in dehydration rat model with glucose supplementation. This was proven by the following results. In dehydration rat model with glucose supplementation, the AUC of OH-CZX was significantly smaller (1900 versus 1050 microg min/ml), AUC(OH-CZX)/AUC(CZX) ratio was considerably smaller (105 versus 34.3%), C(max) was significantly lower (20.6 versus 8.08 microg/ml), total amount excreted in 24-h urine as unchanged OH-CZX was significantly smaller (62.3 versus 42.7% of intravenous dose of CZX), and in vitro V(max) (2.18 versus 1.20 nmol/min/mg protein) and CL(int) (0.0285 versus 0.0171 ml/min/mg protein) were significantly slower than those in dehydration rat model.
Life Sciences 12/2006; 79(23):2179-86. · 2.53 Impact Factor
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ABSTRACT: To test the effect of 72 h water deprivation on the non-renal clearance (CL) of DA-8159 in a rat model of dehydration. DA-8159 is mainly metabolized via CYP3A1/2 and the expression and mRNA level of CYP3A1/2 are not affected by dehydration.
DA-8159 (30 mg/kg) was administered intravenously or orally to male control Sprague Dawley rats and rat model of dehydration.
As expected, after intravenous administration, the CL(NR) values of DA-8159 were comparable between two groups of rats. This could be supported by comparable intrinsic CL of DA-8159 using hepatic microsomes for both groups of rats. However, the CL was significantly slower in rat model of dehydration due, at least in part, to significantly slower renal CL in rat model of dehydration. The slower CL(R) in rat model of dehydration could be due to urine flow ratedependent renal CL of DA-8159; the less urine output, the less the urinary excretion of unchanged DA-8159. After oral administration, the AUC values of DA-8159 were not significantly different between two groups of rats, although the AUC of DA-8159 in rat model of dehydration was significantly greater than controls after intravenous administration. This could be possibly due to changes in the intestinal first-pass effects in rat model of dehydration.
After intravenous administration of DA-8159, the non-renal CL values were comparable between two groups of rats due to the lack of effect of dehydration on CYP3A1/2.
Journal of pharmacy & pharmaceutical sciences: a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 02/2006; 9(1):10-21. · 1.65 Impact Factor
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ABSTRACT: Pharmacokinetic parameters of theophylline and one of its metabolites, 1,3-dimethyluric acid (1,3-DMU), were compared after intravenous and oral administration of aminophylline, 5mg/kg as theophylline, to diabetes mellitus rats induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. In DMIA and DMIS rats, expression of CYP1A2 and 2E1 increased approximately three times. Theophylline was metabolized to 1,3-DMU by CYP1A2 and 2E1 in rats. Hence, it was expected that formation of 1,3-DMU increased in DMIA or DMIS rats. This was proven by the following results. First, after intravenous administration of theophylline, the AUC of 1,3-DMU was significantly greater in DMIA (110% increase) or DMIS (47.4% increase) rats. Second, the AUC of theophylline was significantly smaller in DMIA (26.1% decrease) or DMIS (30.1% decrease) rats because of significantly faster time-averaged total body clearance in DMIA (34.8% increase) or DMIS (42.7% increase) rats. Third, based on in vitro hepatic microsomal studies, intrinsic 1,3-DMU formation clearances were significantly faster in DMIA (20.4% increase) or DMIS (30.7% increase) rats than respective control rats. Similar results (AUC values of theophylline and 1,3-DMU) were also obtained after oral administration.
European Journal of Pharmaceutical Sciences 10/2005; 26(1):114-23. · 3.21 Impact Factor
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ABSTRACT: A high-performance liquid chromatographic method using liquid-liquid extraction was developed for the determination of 1-(3-fluoro-4-hydroxy-5-mercaptomethyl-tetrahydrofuran-2-yl)-5-methyl-1H-pyrimidine-2,4-dione (l-FMAUS; I) in rat plasma and urine. A 100 microl aliquot of distilled water containing l-cysteine (100 mg/ml) was added to a 100 microl aliquot of biological sample. l-Cysteine was employed to protect binding between the 5'-thiol of I and protein in the biological sample. After vortex-mixing for 30s and adding a 50 microl aliquot of the mobile phase containing the internal standard (10 microg/ml of 3-aminophenyl sulfone), 1 ml of ethyl acetate was used for extraction. After vortex-mixing, centrifugation, and evaporating the ethyl acetate, the residue was reconstituted with a 100 microl aliquot of the mobile phase. A 50 microl aliquot was injected onto a C(18) reversed-phase column. The mobile phases, 50 mM KH(2)PO(4) (pH = 2.5):acetonitrile (85:15, v/v) for rat plasma and 50 mM KH(2)PO(4) (pH 2.5):acetonitrile:methanol (85:10:5, v/v/v) for urine samples, were run at a flow-rate of 1.2 ml/min. The column effluent was monitored by an ultraviolet detector set at 265 nm. The retention times for I and the internal standard were approximately 9.7 and 12.5 min, respectively, in plasma samples and the corresponding values in urine samples were 16.8 and 14.9 min. The quantitation limits of I in rat plasma and urine were 0.1 and 0.5 microg/ml, respectively.
Journal of Chromatography B 05/2004; 803(2):367-70. · 2.89 Impact Factor
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ABSTRACT: In this letter, we introduce a new proxy that effectively prevents unnecessary retransmissions from flowing over a wireless link on a path with sudden delay. The proposed Spurious Timeout (STD) algorithm detects spurious timeout based on the data and acknowledge sequence number. It responses to spurious timeout by filtering duplicate acknowledgements that can cause spurious fast retransmission. Simulation results show that the proposed STD algorithm performs better than, or as well as, other end-to-end mechanisms.
IEEE Communications Letters 02/2004; 8(1):30- 32. · 0.98 Impact Factor
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ABSTRACT: The effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of torasemide were evaluated in rabbits. Each rabbit received 2-h constant intravenous infusion of 1 mg kg(-1) torasemide with 0% replacement (treatment 1, n=6), 50% replacement (treatment 2, n=9), 100% replacement with lactated Ringer's solution (treatment 3, n=8), and 100% replacement with 5% dextrose in water (treatment 4, n=6). Total body (4.53, 5.72, 10.0 and 4.45 mL min(-1) kg(-1) for treatments 1-4, respectively) and renal clearance (1.44, 1.87, 6.78 and 1.72 mL min(-1) kg(-1)) of torasemide, and total amount of unchanged torasemide excreted in 8-h urine (A(e 0-8 h): 694, 780, 1310 and 1040 microg) in treatment 3 were considerably faster and greater compared with treatments 1, 2 and 4. Although the difference in A(e 0-8 h) between treatments 1 and 3 was only 88.8%, the diuretic and/or natriuretic effects of torasemide were markedly different among the four treatments. For example, the mean 8-h urine output was 101, 185, 808 and 589 mL for treatments 1-4, respectively, and the corresponding values for sodium excretion were 10.1, 20.6, 89.2 and 29.9 mmol, and for chloride excretion were 14.5, 27.9, 94.0 and 37.2 mmol. Although full fluid replacement was used in both treatments 3 and 4, the 8-h diuretic, natriuretic and chloruretic effects in treatment 3 were significantly greater compared with treatment 4, indicating the importance of the composition of fluid replacement. Both treatments 1 and 4 received no sodium replacement, however, the 8-h diuretic, natriuretic and chloruretic effects were significantly greater in treatment 4 compared with treatment 1, indicating the importance of rate of fluid replacement for the diuretic effects. Therefore, the 8-h diuretic, natriuretic and chloruretic effects were significantly greater in treatment 3 compared with treatments 1, 2 and 4, indicating the importance of full fluid and electrolyte replacement. Some implications for the bioequivalence evaluation of dosage forms of torasemide are discussed.
Journal of Pharmacy and Pharmacology 12/2003; 55(11):1515-22. · 2.17 Impact Factor
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ABSTRACT: In this paper, we propose a new algorithm that aids the recovery of lost packets by generating additional duplicate ACK. It is shown that by adopting this algorithm the response time and throughput of short term bursty traffic can be improved in a wireless link with high error rate.
Vehicular Technology Conference, 2002. VTC Spring 2002. IEEE 55th; 02/2002
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ABSTRACT: In this letter, we introduce a new proxy that effectively prevents unnecessary retransmissions from flowing over a wireless link on a path with sudden delay. The proposed Spurious Timeout (STD) algorithm detects spurious timeout based on the data and acknowledge sequence number. It responses to spurious timeout by filtering duplicate acknowledgements that can cause spurious fast retransmission. Simulation results show that the proposed STD algorithm performs better than, or as well as, other end-to-end mechanisms.
