Article Publish Status: FREE
Abstract Title:

Influence of cancer cachexia on drug liver metabolism and renal elimination in rats.

Abstract Source:

J Cachexia Sarcopenia Muscle. 2015 Mar ;6(1):45-52. PMID: 26136411

Abstract Author(s):

Katja Cvan Trobec, Mojca Kerec Kos, Jurij Trontelj, Iztok Grabnar, Anika Tschirner, Sandra Palus, Stefan D Anker, Jochen Springer, Mitja Lainscak

Article Affiliation:

Katja Cvan Trobec

Abstract:

BACKGROUND: Body wasting and cachexia change body composition and organ function, with effects on drug pharmacokinetics. The aim of this study was to investigate how cancer and cancer cachexia modify liver metabolism and renal drug elimination in rats.

METHODS: Nine male Wistar-Han rats received a single oral dose of midazolam and propranolol (markers of hepatic metabolism), and 10 rats received single intravenous dose of iohexol, a marker of glomerular filtration rate. After drug delivery, multiple dried blood samples were obtained within 2 h post-dose to evaluate drug pharmacokinetic profiles. After baseline sampling (D0), rats were injected with tumour cells. Drug application and blood sampling were repeated when rats developed tumours (Day 5-D5), and when rats were severely cachectic (Day 10-D10). Clearance (CL) and volume of distribution (Vd) of drugs were assessed with non-linear mixed effects modelling. Weight and body composition were measured on D0 and D10 and were related to pharmacokinetic parameters.

RESULTS: All three drugs showed non-significant trend towards increased CL and Vd on D5. On D10, midazolam and propranolol CL and midazolam Vd significantly decreased from baseline (-80.5%, -79.8%, and -72.0%, respectively, P < 0.05 for all). Iohexol CL decreased by 29.8% from baseline value on D10, which was related to body weight loss (Pearson's r = 0.837, P = 0.019).

CONCLUSIONS: Hepatic metabolism and renal drug elimination are significantly reduced in cachexia, which could increase risk of dose-related adverse events.

Study Type : Animal Study

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2020 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.