Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent, in rats.

1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.

Effects of ACE and ADD1 gene polymorphisms on blood pressure response to hydrochlorothiazide: a meta-analysis.

Hydrochlorothiazide (HCTZ) is used to treat uncomplicated hypertension. However, many studies have reported the variance of inter-individual response to HCTZ. A meta-analysis of published data was conducted to evaluate the pharmacogenetic associations of ACE I/D and ADD1 Gly460Trp polymorphisms with blood pressure changes during HCTZ therapy.

Effects of 17α-ethynylestradiol-induced cholestasis on the pharmacokinetics of doxorubicin in rats: reduced biliary excretion and hepatic metabolism of doxorubicin.

1. Since the prevalent hormonal combination therapy with estrogen analogues in cancer patients has frequency and possibility to induce the cholestasis, the frequent combination therapy with 17α-ethynylestradiol (EE, an oral contraceptive) and doxorubicin (an anticancer drug) might be monitored in aspect of efficacy and safety. Doxorubicin is mainly excreted into the bile via P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in hepatobiliary route and metabolized via cytochrome P450 (CYP) 3A subfamily.

Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor.

Tamoxifen, which is used to treat breast cancer, and ondansetron, used for the treatment of chemotherapy-induced nausea, are commonly metabolized via cytochrome P450 (CYP) 2D subfamily and 3A1/2 in rats, as in humans. This study was conducted to investigate the pharmacokinetic interactions between ondansetron and tamoxifen after intravenous and oral administration of ondansetron (both 8 mg/kg) and/or tamoxifen (2 and 10 mg/kg for intravenous and oral administration, respectively), in rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammarian tumors (DMBA rats), used as an animal model of human breast cancer. The total area under the plasma concentration-time curve, from time zero to infinity (AUC) of tamoxifen was significantly greater after both intravenous and oral administration with ondansetron, compared to that after administration of tamoxifen-alone.

Effects of morin on the pharmacokinetics of etoposide in 7,12-dimethylbenz[a]anthracene-induced mammary tumors in female Sprague-Dawley rats.

Etoposide, used for the treatment of breast cancer, is mainly metabolized via hepatic cytochrome P450 (CYP) 3A4 in humans and is also a substrate for p-glycoprotein (P-gp). Morin is known to be able to modulate the activities of metabolic enzymes including CYPs and can act as a potent P-gp inhibitor. The purpose of this study was to investigate the effects of morin on the pharmacokinetics of etoposide in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors.

Effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition.

Protein-calorie malnutrition (PCM) could occur frequently in cancer patients and alter the pharmacokinetics of drugs. Also cysteine shows anti-oxidative effect and changes the activities of drug metabolizing enzyme and/or transporters. Herein, we investigated the effects of cysteine on the pharmacokinetics of tamoxifen in rats with protein-calorie malnutrition (PCM).

Reduced clearance of ε-acetamidocaproic acid in rats with acute renal failure induced by uranyl nitrate.

Objectives: Anti-ulcer drugs are frequently used in patients with acute renal failure (ARF). Zinc acexamate is ionized to zinc and ε-acetamidocaproic acid and free EACA exerts a potent therapeutic effect in treating gastric or duodenal ulcers with few side effects. Thus, pharmacokinetic changes in rats with acute renal failure induced by uranyl nitrate (U-ARF rats) were investigated in this study.

Pharmacokinetic interaction between metoprolol and SP-8203 in rats: competitive inhibition for the metabolism of metoprolol by SP-8203 via hepatic CYP2D subfamily.

1. The occurrence of cerebral ischemia is prevalent in patients with hypertension and the combination drug therapy is needed. Thus, the pharmacokinetic interaction between metoprolol (anti-hypertension drug) and SP-8203 (a new drug candidate for cerebral ischemia) with respect to the metabolism via CYP isozymes was evaluated.

Pharmacokinetics of verapamil and its metabolite norverapamil in rats with hyperlipidaemia induced by poloxamer 407.

In this study, the pharmacokinetics of verapamil and its active metabolite norverapamil were evaluated following intravenous and oral administration of 10 mg/kg verapamil to rats with hyperlipidaemia (HL) induced by poloxamer 407 (HL rats). The total area under the plasma concentration time curve (AUC) of verapamil in HL rats following intravenous administration was significantly greater (by 11.2%) than in control rats due to their slower (by 11%) non-renal clearance.

Approaches for predicting human pharmacokinetics using interspecies pharmacokinetic scaling.

Reliably predicting pharmacokinetic behavior in humans from preclinical data is an important aspect of drug development. The most widely used technique in this regard is allometric scaling. In this review, various approaches developed for predicting pharmacokinetic parameters in humans using interspecies scaling are introduced and discussed.

Effects of poloxamer 407-induced hyperlipidemia on the pharmacokinetics of carbamazepine and its 10,11-epoxide metabolite in rats: Impact of decreased expression of both CYP3A1/2 and microsomal epoxide hydrolase.

The pharmacokinetics of carbamazepine (CBZ) and its active 10,11-epoxide metabolite (CBZ-E) were evaluated after intravenous and oral administration of 5 mg/kg CBZ to rats with hyperlipidemia induced by poloxamer 407 (HL rats) and controls. The total area under the plasma concentration-time curve (AUC) of CBZ in HL rats after intravenous administration was significantly greater than that in controls due to their slower non-renal clearance (CL(NR)). This was due to slower hepatic CL(int) for metabolism of CBZ to CBZ-E in HL rats via CYP3A1/2.

Effects of cysteine on the pharmacokinetics of docetaxel in rats with protein-calorie malnutrition.

The objective of this study is to report the effects of cysteine on the pharmacokinetics of intravenous and oral docetaxel in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of docetaxel were assessed using control, CC (control with cysteine), PCM and PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of docetaxel were further investigated through in vitro transport studies using rat intestine and Caco-2 cell monolayers.

Pharmacokinetics and first-pass metabolism of astaxanthin in rats.

Astaxanthin is a carotenoid with antioxidant, anti-cancer and anti-inflammatory properties. The pharmacokinetics of astaxanthin after its intravenous (5, 10, and 20 mg/kg) and oral (100 and 200 mg/kg) administration and its first-pass extraction ratios after its intravenous, intraportal or intragastric (20 mg/kg) administration were evaluated in rats. The pharmacokinetic parameters of astaxanthin were dose dependent after its intravenous administration, due to the saturable hepatic metabolism of astaxanthin, but dose independent after oral administration.

Negligible effect of oral garlic oil on the oral absorption of pyridoxine in metadoxine in rats.

Metadoxine [an ion-pair between pyridoxine and pyrrolidone carboxylate (PCA)] plus garlic oil treatment synergistically reduces alcoholic steatosis compared to each agent alone. We evaluated the effect of garlic oil on the pharmacokinetics of pyridoxine. After the oral administration of metadoxine, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) and the peak plasma concentration (C(max)) of pyridoxine were significantly greater (by 40.

Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541.

Purpose: This study was performed to find which types of hepatic CYP isoforms are responsible for the metabolism of mirodenafil (a new erectogenic) and one of its metabolite, SK3541, using various hepatic CYP inducers and inhibitors in rats.

Methods: Mirodenafil at a dose of 20 mg/kg was administered intravenously to control rats and rats pretreated with various CYP inducers and inhibitors. The disappearance of SK3541 was also measured in vitro hepatic microsomes of rats with and without CYP inducer and inhibitors.

Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury.

Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were assessed.

Therapeutic potential of dithiolethiones for hepatic diseases.

Comprehensive studies support the notion that oltipraz [4-methyl-5-(2-pyrazynyl)-1,2-dithiole-3-thione] and its congeners exert cancer chemopreventive effects by the prevention, inhibition or reversal of carcinogenic processes. Recently, it was found that dithiolethione compounds had the activities to prevent or treat fibrosis, insulin resistance, and mitochondrial protective effects in the liver by a mechanism involving AMP-activated protein kinase (AMPK) and/or 70-kDa ribosomal protein S6 kinase 1 (S6K1). Moreover, chemical regulation of the AMPK-S6K1 pathway was found to affect Liver X receptor (LXR) activity and lipogenesis, leading to the identification of AMPK and S6K1 as targets for treating hepatic steatosis.

Pharmacokinetic interaction between tamoxifen and ondansetron in rats: non-competitive (hepatic) and competitive (intestinal) inhibition of tamoxifen metabolism by ondansetron via CYP2D subfamily and 3A1/2.

Purpose: Tamoxifen and ondansetron were commonly metabolized via rat hepatic CYP2D subfamily and 3A1/2, and ondansetron is used to treat chemotherapy-induced nausea. The purpose of this study was to report the pharmacokinetic interaction between tamoxifen and ondansetron in rats.

Methods: The pharmacokinetics of tamoxifen and ondansetron were evaluated after the intravenous and oral administration of tamoxifen, ondansetron, and both drugs together to rats.

Pharmacokinetic interaction between oltipraz and silymarin in rats.

Purpose: To evaluate the pharmacokinetic interaction between oltipraz and silymarin after intravenous and oral administration of both drugs to male Sprague-Dawley rats.

Methods: Oltipraz (single doses of 10 and 30 mg/kg for intravenous and oral administration, respectively), silymarin (single doses of 50 and 100 mg/kg for intravenous and oral administration, respectively, and 14 days oral administration of 100 mg/kg), alone and together were administered to control rats.

Results: The pharmacokinetic parameters of oltipraz did not significantly altered by silymarin.

Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase-II enzymes.

Liquiritigenin (LQ), an active component of licorice, has an inhibitory effect on LPS-induced inhibitory nitric oxide synthase expression. This study investigated the effects of LQ on choleresis, the expression of hepatic transporters and phase-II enzymes, and fulminant hepatitis. The choleretic effect and the pharmacokinetics of LQ and its glucuronides were monitored in rats.

Effects of endotoxin derived from Escherichia coli lipopolysaccharide on the pharmacokinetics of drugs.

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an animal model of chronic inflammation such as sepsis. During inflammation, development of diarrhea, and changes in the plasma protein bindings, in the hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal excretion of drugs have been reported.

Effects of water deprivation on drug pharmacokinetics: correlation between drug metabolism and hepatic CYP isozymes.

Male Sprague-Dawley rats deprived of water for 72 h (a rat model of dehydration) showed no change in protein expression of the hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2C11, or 3A1/2, but an increase in protein expression (3-fold) and mRNA level (2.6-fold) of CYP2E1. Glucose feeding instead of food normalized CYP2E1 protein expression during dehydration.

Pharmacokinetic changes of drugs in rat model of acute renal failure induced by uranyl nitrate: correlation between drug metabolism and hepatic microsomal cytochrome P450 isozymes.

In male Sprague-Dawley rat model of acute renal failure induced by uranyl nitrate (rat model of U-ARF), the expression of CYP2C11 decreased by 20% of control, whereas that of CYP2E1 and 3A1(23) increased 2-4 and 4 times, respectively, as compared with controls. The expressions of CYPIA2 and 2B1/2 were not changed by U-ARF. The mRNA level of CYP2E1 increased 3 times and that of CYP2C11 decreased to 25% of controls.

Dose-dependent pharmacokinetics of telithromycin after intravenous and oral administration to rats: contribution of intestinal first-pass effect to low bioavailability.

Purpose: To evaluate the pharmacokinetics of telithromycin after intravenous and oral administration and to find the reason for incomplete F value (first pass-effect) after intravenous, intraportal, intragastric, and intraduodenal administration to rats.

Methods: Telithromycin was administered intravenously or orally at doses of 20, 50, and 100 mg/kg to rats. And hepatic, gastric, and intestinal first-pass effects of telithromycin were also measured after intravenous, intraportal, intragastric, and intraduodenal administration at a dose of 50 mg/kg to rats.

Effects of glucose supplementation on the pharmacokinetics of intravenous chlorzoxazone in rats with water deprivation for 72 h.

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.