Metabolism of [14C]paraldehyde in mice in vivo, generation and trapping of acetaldehyde.

The metabolic fate and the kinetics of paraldehyde metabolism after the i.p. administration of a 400 mg/kg dose of this agent were investigated in mice. Paraldehyde was found to have a biologic half-life in this species of 41.5 min, its disappearance from blood being governed by a single component exponential process with a rate constant of 0.0167 min-1. By using [14C]paraldehyde, it was found that the major process responsible for paraldehyde disappearance was its metabolic degradation to carbon dioxide, a two-step process; the first step of which was inhibited by pretreatment with SKF-525A. The rate constants for the two steps being 0.0121 and 0.0212 min-1, respectively; on the basis of these rate constants it was calculated this pathway would account for 72.3% of the administered dose at infinite time. A second major pathway for the disposition of paraldehyde was its excretion in expired air, which, at infinite time, would account for 9.6% of the dose. No acetaldehyde (AcH) could be detected in either the breath or the blood of mice after paraldehyde administration. Pretreatment with the aldehyde dehydrogenase inhibitors, pargyline or cyanamide, did not result in the accumulation or excretion of detectable amounts of AcH. Pretreatment of mice administered [14C]paraldehyde with both cyanamide and D-penicillamine,, an AcH sequestering agent, resulted, however, in urinary excretion of the 14C-labeled condensate of D-penicillamine and AcH showing AcH to be formed from paraldehyde. The above results indicate that paraldehyde is rapidly metabolized in vivo to carbon dioxide and that AcH is an intermediary product in this process.