Pharmacokinetics of intravenous chlorzoxazone in rats with dehydration and rehydration: effects of food intakes

Kim, Yu C.; Kim, Yoon G.; Kim, Eun J.; Cho, Min K.; Kim, Sang G.; Lee, Myung G.

doi:10.1002/bdd.335

Cited by 7 publications

(13 citation statements)

References 20 publications

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“…Similar results were also obtained from other rat studies [7]. Food intake also decreased significantly in the rat model of dehydration (Tables 1, 3 and 4) and similar results were also reported from other rat studies [6,7,10,11,23,24]. The smaller body weight gain in the rat model of dehydration could be due to the lower food intake to prevent elevations in the extracellular fluid osmolarity and sodium concentration [6] in addition to water deprivation.…”

Section: Discussionsupporting

confidence: 92%

Effects of water deprivation on the pharmacokinetics of metformin in rats

Choi

Lee

2007

Biopharm & Drug Disp

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It was reported that metformin was mainly metabolized via hepatic CYP2C11, 2D1 and 3A1/2 in rats, and in a rat model of dehydration, the expressions of hepatic CYP2C11 and 3A1/2 were not changed. Hence, it could be expected that the Cl(nr) of metformin is comparable between two groups of rats if the contribution of CYP2D1 in the rat model of dehydration is not considerable. It was also reported that the timed-interval renal clearance of metformin was dependent on the urine flow rate in rats. In the rat model of dehydration, the 24 h urine output was significantly smaller than in the controls. Hence, the urinary excretion of metformin was expected to be smaller than the controls. The above expectations were proven as follows. After intravenous administration of metformin (100 mg/kg) to the rat model of dehydration, the Cl(nr) were comparable between the two groups of rats. After both intravenous and oral administration of metformin (both 100 mg/kg) to the rat model of dehydration, the 24 h urinary excretion of the drug was significantly smaller than in the controls. After oral administration of metformin to the rat model of dehydration, the AUC was significantly greater (99.2% increase) than the controls.

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Section: Discussionsupporting

confidence: 92%

Effects of water deprivation on the pharmacokinetics of metformin in rats

Choi

Lee

2007

Biopharm & Drug Disp

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“…This indicated that DA-7867 was mainly reabsorbed in the renal tubules for both groups of rats. The renal extraction ratios of DA-7867 (Cl r of DA-7867/ kidney plasma flow rate; only for urinary excretion of unchanged DA-7867) were estimated based on Cl r (Table 2), hematocrit [25] and kidney blood flow rate in control rats, 36.8 ml/min/kg [35], and in the rat model of dehydration [36]. After 8 days of water deprivation in rats, the renal blood flow rate reduced by 65% [36].…”

Section: Discussionmentioning

confidence: 99%

“…Water was not supplied during the experimental period in the rat model of dehydration, since this will cause partial rehydration in the rat model of dehydration. It was reported that supplying water in the rat model of dehydration (rehydration) causes pharmacokinetic changes of chlorzoxazone [25] and tissue distribution changes of gentimicin in rats [14] compared with those in the rat model of dehydration. Approximately a 0.12 ml aliquot of blood was collected via the carotid artery at 0 (to serve as a control), 1 (at the end of the infusion), 5,30,60,90,120,180,240,360,480,720,960 and 1440 min after intravenous administration of DA-7867.…”

Section: Intravenous Studymentioning

confidence: 99%

Effects of water deprivation for 72 hours on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats

Bae

Kim

Lee

et al. 2006

Biopharm. Drug Dispos.

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The pharmacokinetic parameters of DA-7867 were compared after intravenous and oral administration at a dose of 10 mg/kg in control rats and in rats with water deprivation for 72 h (rat model of dehydration). After intravenous administration in the rat model of dehydration, the Cl(nr) (0.654 versus 0.992 ml/min/kg) and Cl(r) (0.0273 versus 0.0784 ml/min/kg) values were significantly slower than in the controls. The slower Cl(nr) could be due mainly to a significantly smaller total amount of unchanged DA-7867 recovered from the gastrointestinal tract at 24 h (GI(24 h): 5.16% versus 9.21% of intravenous dose) due to impaired liver function in the rat model of dehydration. The slower Cl(r) could be due mainly to a significantly smaller 24 h urinary excretion of unchanged drug (Ae(0-24 h): 4.41% versus 7.75% of intravenous dose) due to urine flow rate-dependent Cl(r) of DA-7867 in the rat model of dehydration. Hence, the Cl was significantly slower in the rat model of dehydration (0.677 versus 1.07 ml/min/kg). After intravenous administration in the rat model of dehydration, the V(ss) of DA-7867 was significantly smaller than in the controls (396 versus 506 ml/kg) due mainly to significantly smaller free (unbound to plasma proteins) fractions of DA-7867 in plasma (6.90% versus 29.2%) in the rat model of dehydration. After oral administration in the rat model of dehydration, the AUC was significantly greater than that in controls (10800 versus 7060 microg min/ml) due mainly to a significantly smaller Ae(0-24 h) than in controls (3.50% and 6.17% of oral dose).

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“…The 0.9% NaCl-injectable solution was infused at rates of 0.3-1.5 ml/min to control the urine flow rate. Note that this experiment could not be performed in the rat model of dehydration, because rehydration of 48 h water-deprived rats for the next 24 h caused partial restoration of the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of intravenous chlorzoxazone (metabolized to 6-hydroxychlorzoxazone via CYP2E1 in rats) in rat model of water deprivation to the controls [16].…”

Section: Ratsmentioning

confidence: 99%

Effects of water deprivation on the pharmacokinetics of theophylline and one of its metabolites, 1,3‐dimethyluric acid, after intravenous and oral administration of aminophylline to rats

Choi

Kang

Chung

et al. 2007

Biopharm & Drug Disp

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It has been reported that the expressions of hepatic microsomal cytochrome P450 (CYP) 1A1/2, 2B1/2 and 3A1/2 were not changed in rats with water deprivation for 72 h (rat model of dehydration) compared with the controls. It has been also reported that 1,3-dimethyluric acid (1,3-DMU) was formed from theophylline via CYP1A1/2 in rats. Hence, it could be expected that the formation of 1,3-DMU could be comparable between the two groups of rats. As expected, after both intravenous and oral administration of theophylline at a dose of 5 mg/kg to the rat model of dehydration, the AUC of 1,3-DMU was comparable to the controls. After both intravenous and oral administration of theophylline to the rat model of dehydration, the Cl(r) of both theophylline and 1,3-DMU was significantly slower than the controls. This could be due to significantly smaller urinary excretions of both theophylline and 1,3-DMU since the AUC of both theophylline and 1,3-DMU were comparable between the two groups of rats. The smaller urinary excretion of both theophylline and 1,3-DMU could be due to urine flow rate-dependent timed-interval renal clearance of both theophylline and 1,3-DMU in rats.

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Pharmacokinetics of intravenous chlorzoxazone in rats with dehydration and rehydration: effects of food intakes

Cited by 7 publications

References 20 publications

Effects of water deprivation on the pharmacokinetics of metformin in rats

Effects of water deprivation on the pharmacokinetics of metformin in rats

Effects of water deprivation for 72 hours on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats

Effects of water deprivation on the pharmacokinetics of theophylline and one of its metabolites, 1,3‐dimethyluric acid, after intravenous and oral administration of aminophylline to rats

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