Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase isozymes by repeated cyanamide administration: Pharmacokinetic-pharmacodynamic relationships
✍ Scribed by Dr Juan Pruñonosa Piera; Rosendo Obach; Maria Luisa Sagristá; Jorge Bozal
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 530 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The inhibition of rat hepatic mitochondria1 aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra-peritoneal cyanamide administration. The low-K, mitochondria1 ALDH isozyme was more susceptible to cyanamide-induced inhibition (DIs0 = 0.104 mg kgl) than the high-K, isozyrne (DI,,= 8.52 mg kg-I), with almost complete inhibition occurring at 0.35 mg kg-' total cyanamide administered for the low-K, isozyrne. The relationships between plasma and liver cyanamide concentrations and the inhibition of high-K, ALDH were established by means of the sigmoid I,, 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.