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Biomedical subjects

John Paul Fawcett

Publications and source records attributed to John Paul Fawcett.

3 recordsLinked to original sources
PubMed2005

Characterization of the pharmacokinetics of dioscin in rat.

Dioscin (diosgenyl 2,4-di-O-alpha-l-rhamnopyranosyl-beta-d-glucopyranoside) is an important constituent of some traditional Chinese medicines with several bioactivities. We have investigated the pharmacokinetics of dioscin in rat after intravenous and oral administrations. Compartmental methods were used to perform pharmacokinetic data analysis. The dose-dependent pharmacokinetics of dioscin was characterized after intravenous administrations (0.064, 0.16, 0.4 and 1.0mg/kg) to rats. There was significant decrease in clearance with increasing dose (4.67+/-0.09 ml/min/kg (0.064 mg/kg) versus 3.49+/-0.23 ml/min/kg (1.0 mg/kg), P<0.05), and the plot of reciprocal clearance values versus the doses was linear (r=0.909, P<0.05). After an I.V. dose of 1mg/kg, simultaneous oral gavage of activated charcoal did not change the pharmacokinetic parameters indicating enterohepatic recycling of dioscin is not important in rat. The absolute oral bioavailability was very low (0.2%). In tissue distribution and bile excretion studies after I.V. and oral administrations, dioscin was shown to undergo a prolonged absorption from the intestinal tract and slow elimination from organs, and only a small amount of drug was recovered in bile. The cumulative amounts of dioscin in feces and urine indicated that the parent drug is mainly excreted in the feces.

Administration, Oral↗
PubMed2003

Decrease in hepatic drug-metabolizing enzyme activities after removal of rats from pine bedding.

Wood is often used as a contact bedding material for laboratory animals. It has been established that wood, particularly softwood, has the potential to induce hepatic drug-metabolizing enzymes. However, to the authors' knowledge, changes in enzyme activity after removal of animals from bedding have not been characterized. The purpose of the study reported here was to determine how hepatic ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities alter over time after removal of rats from pine bedding. Male rats, three to four months old, raised in cages containing pine bedding, were transferred to wire-bottomed cages. At various times thereafter (up to 84 days), groups of rats were euthanized and the liver was processed to obtain microsomes. The microsomal protein and total cytochrome P450 (CYP) content and enzyme activities were determined. Significant differences in total microsomal protein or total CYP values were not observed over the 84 days, but a decrease in ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities was detected. For p-nitrophenol hydroxylation, the decrease was exponential, with a half-life of approximately nine days, whereas for ethoxyresorufin-O-deethylation, a rapid decrease in activity in the first week was followed by a reduced rate of decrease thereafter. Enzyme activities did not stabilize for at least six weeks. Researchers using laboratory animals should, therefore, be aware that it takes several weeks for enzyme activities to stabilize once animals are removed from the bedding.

Animals↗