Related Experiment Video
Updated: Aug 10, 2026

The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase isozymes by repeated cyanamide administration:
J Pruñonosa Piera1, R Obach, M L Sagristá
1Department of Biochemistry and Physiology, Faculty of Chemistry, University of Barcelona, Spain.
Abstract:
The inhibition of rat hepatic mitochondrial aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra-peritoneal cyanamide administration. The low-Km mitochondrial ALDH isozyme was more susceptible to cyanamide-induced inhibition (DI50 = 0.104 mg kg-1) than the high-Km isozyme (DI50 = 8.52 mg kg-1), with almost complete inhibition occurring at 0.35 mg kg-1 total cyanamide administered for the low-Km isozyme. The relationships between plasma and liver cyanamide concentrations and the inhibition of high-Km ALDH were established by means of the sigmoid Imax model. The effect of dosing rate on the plasma concentration of cyanamide at apparent steady-state showed non-linearity, indicating that clearance or first-pass metabolism of cyanamide during its absorption after intraperitoneal administration did not remain constant throughout the range of doses studied.
Related Concept Videos
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Drug Toxicity: Dose-Dependent Reactions

