Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride

Khemawoot, Phisit; Maruyama, Chiharu; Tsukada, Hirotaka; Noda, Hidetoshi; Ishizaki, Junko; Yokogawa, Koiçhi; Miyamoto, Ken‐ichi

doi:10.1002/bdd.563

Cited by 12 publications

(7 citation statements)

References 19 publications

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“…In some cases, the drug metabolizing enzymes may be induced by the presence of liver disease (Aweeka et al, 1999;Lu & Cederbaum, 2008), whereas Igarza et al (2006Igarza et al ( , 2004Igarza et al ( , 2002, Bengtsson et al (1997) and Girard and Matte (1995) Rule et al (1996) and Nouws et al (1983) in other cases, they can be inhibited (Orlando et al, 2006). In addition to these more obvious effects of liver disease, hepatic dysfunction can also lead to changes in plasma protein binding (e.g., Klammt et al, 2008), intestinal absorption (Takaya et al, 1989;Khemawoot et al, 2007), and decreased renal perfusion and glomerular filtration (Gundling et al, 2008).…”

Section: Hepatic Impairmentmentioning

confidence: 99%

Patient variation in veterinary medicine: part I. Influence of altered physiological states

Martinez

Modrić

2010

Journal of Veterinary Pharmacology and Therapeutics

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Martinez, M., Modric, S. Patient variation in veterinary medicine: part I. Influence of altered physiological states. J. vet. Pharmacol. Therap.33, 213–226. In veterinary medicine, the characterization of a drug’s pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter the outcome of PK studies and therefore potentially alter the pharmacological response. Some of these factors are easily identified, such as breed, gender, age, and body weight. Others are less obvious, such as disease, heritable traits, and environmental factors. This manuscript provides an overview of the various stressors (such as disease, inflammation, pregnancy, and lactation) that can substantially alter drug PK. Part II of this series provides an overview of the potential impact of physiological variables such as age, weight, and heritable traits, on drug PK. Ultimately, failure to identify appropriate covariates can lead to substantial error when predicting the dose–exposure relationship within a population.

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Section: Hepatic Impairmentmentioning

confidence: 99%

Patient variation in veterinary medicine: part I. Influence of altered physiological states

Martinez

Modrić

2010

Journal of Veterinary Pharmacology and Therapeutics

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“…In male SD rats, exposure to carbon tetrachloride (640 mg/kg per 2 days for 45 days) in a long-term treatment decreases hepatic Mrp2 mRNA expression (Okumura et al, 2007). In rats with chronic hepatic failure induced by carbon tetrachloride (1.0 mg/kg, subcutaneously; s.c., 3 times per week) for 2 or 3 months, Mrp2 mRNA expression was significantly lower than in the control group (Khemawoot et al, 2007). …”

Section: Regulation Of Hepatic Abcc2/mrp2 Transporters By Xenobioticsmentioning

confidence: 67%

Regulation of hepatic ABCC transporters by xenobiotics and in disease states

Manautou

2010

Drug Metabolism Reviews

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The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules.

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“…Khemawoot et al . reported that the enzyme activity of UDP‐glucuronosyltransferase in the liver of rats treated with CCl 4 decreased significantly 11. In addition, the cytosolic glutathione S‐transferase activities were markedly decreased following the development of CCl 4 ‐alcohol‐induced liver fibrosis 12.…”

Section: Resultsmentioning

confidence: 99%

Hepatic fibrosis does not affect the pharmacokinetics of 5‐fluorouracil in rats

Nagata

Hidaka

Hatakeyama

et al. 2010

Biopharm & Drug Disp

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In the case of cancer chemotherapy for hepatocellular carcinoma, 5-fluorouracil (5-FU) is used widely, and has typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and to reduce systemic toxicity. 5-Fluorouracil is eliminated primarily by the liver, and so its use in patients with hepatic disease can be difficult. This study investigated the effect of hepatic fibrosis on the pharmacokinetics of 5-FU in rats. Experimental hepatic fibrosis was induced by carbon tetrachloride treatment. 5-fluorouracil was infused for 15 min into the hepatic artery or the saphenous vein of the rats at a dose of 1.25 mg/kg. There were no significant differences in the plasma concentration and AUC of 5-FU between hepatic disease rats and their controls after both intravenous and intraarterial injection. This result is probably attributed to the fact that there were no significant differences in hepatic blood flow and dihydropyrimidine dehydrogenase (DPD; an initial and rate-limiting enzyme in 5-FU catabolism) activity between hepatic disease rats and their controls, because the total clearance of 5-FU after intravenous and intraarterial administration is mainly limited by hepatic blood flow and DPD activity, respectively. In conclusion, the pharmacokinetics of 5-FU is not affected by hepatic fibrosis, unlike that of many hepatically metabolized drugs.

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Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride

Cited by 12 publications

References 19 publications

Patient variation in veterinary medicine: part I. Influence of altered physiological states

Patient variation in veterinary medicine: part I. Influence of altered physiological states

Regulation of hepatic ABCC transporters by xenobiotics and in disease states

Hepatic fibrosis does not affect the pharmacokinetics of 5‐fluorouracil in rats

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