The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after a single po dose of [14C]cisapride in dogs and humans. The excretion of radioactivity amounted to 97% within 4 days after a 1 mg/kg dose in dogs (72% in feces and 25% in urine). After a 10-mg dose in humans, 44% was excreted in the 0-24-hr urine and 37% in the 0-35-hr feces; excretion was complete within 4 days. Excretion of the parent drug was greater in dogs (0.4-1.3% of the dose in urine, 23% in feces) than in humans (0.2% in urine, 4-6% in feces). This was due, at least in part, to a larger proportion of amine glucuronidation and sulfation in dogs. N-Deal-kylation at the piperidine nitrogen resulting in the main urinary metabolite, norcisapride, and aromatic hydroxylation of the 4-fluorophenyl ring were major metabolic pathways in both species. Norcisapride excretion accounted for 14% of the dose in dogs and 41-45% in humans. Minor metabolic pathways were O-dealkylation at the 4-fluorophenoxy group and piperidine oxidation. Peak plasma levels and AUC values of norcisapride in humans were 8-9 times lower than those of cisapride. Apart from more amine conjugation in dogs, the biotransformation of cisapride was similar in dogs and humans.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Peripheral Serotonin Controls Dietary Fat Absorption and Chylomicron Secretion via 5-HT4 Receptor in Males.
Endocrinology
August 2024
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Postprandial dyslipidemia is commonly present in people with type 2 diabetes and obesity and is characterized by overproduction of apolipoprotein B48-containing chylomicron particles from the intestine. Peripheral serotonin is emerging as a regulator of energy homeostasis with profound implications for obesity; however, its role in dietary fat absorption and chylomicron production is unknown. Chylomicron production was assessed in Syrian golden hamsters by administering an olive oil gavage and IP poloxamer to inhibit lipoprotein clearance.
View Article and Find Full Text PDFIn vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment.
Toxicol Sci
September 2024
Center for Biomedical Engineering, School of Engineering, Brown University, Providence, RI 02912, United States.
Proarrhythmic cardiotoxicity remains a substantial barrier to drug development as well as a major global health challenge. In vitro human pluripotent stem cell-based new approach methodologies have been increasingly proposed and employed as alternatives to existing in vitro and in vivo models that do not accurately recapitulate human cardiac electrophysiology or cardiotoxicity risk. In this study, we expanded the capacity of our previously established 3D human cardiac microtissue model to perform quantitative risk assessment by combining it with a physiologically based pharmacokinetic model, allowing a direct comparison of potentially harmful concentrations predicted in vitro to in vivo therapeutic levels.
View Article and Find Full Text PDFSalidroside modulates repolarization through stimulating Kv2.1 in rats.
Eur J Pharmacol
August 2024
Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Research Service Office, Meishan Hospital of Chengdu University of Traditional Chinese Medicine, Meishan, 620000, China. Electronic address:
Background: Voltage-gated potassium (Kv) channel growth is strongly associated with the development of arrhythmia. Salidroside (Sal), an active component from Rhodiola crenulata, has been shown to exert protective effects against heart disease. The present study was conducted to investigate the effects of Sal on Kv2.
View Article and Find Full Text PDFThe Strength of hERG Inhibition by Erythromycin at Different Temperatures Might Be Due to Its Interacting Features with the Channels.
Molecules
July 2023
Chinese Herb Medicine Division, Zhejiang Agriculture and Forestry University, 666 Wusu Street, Hangzhou 311300, China.
Erythromycin is one of the few compounds that remarkably increase ether-a-go-go-related gene (hERG) inhibition from room temperature (RT) to physiological temperature (PT). Understanding how erythromycin inhibits the hERG could help us to decide which compounds are needed for further studies. The whole-cell patch clamp technique was used to investigate the effects of erythromycin on hERG channels at different temperatures.
View Article and Find Full Text PDFCisapride induced hypoglycemia the KCNH6 potassium channel.
Front Endocrinol (Lausanne)
November 2022
Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Mutations in has been proved to cause hypoinsulinemia and diabetes in human and mice. Cisapride is a stomach-intestinal motility drug used to treat gastrointestinal dysfunction. Cisapride has been reported to be a potential inhibitor of the KCNH family, but it remained unclear whether cisapride inhibited KCNH6.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!