Abstract
AbstractA high incidence of abortion was produced in Duroc pigs (Sus scrofa) by maternal treatment during organogenesis with 5.5 mg/kg chlorcyclizine. The same dose of chlorcyclizine or hydroxyzine administered to pregnant rhesus monkeys (Macaca mulatta) also resulted in a high frequency of abortion. Species differences in the rate of chlorcyclizine metabolism were shown to exist. Chlorcyclizine was administered to nonpregnant rats, monkeys, and pigs on consecutive days, at teratogenic or abortive doses, and blood levels of norchlorcyclizine, the demethylated derivative of chlorcyclizine, were used as an indication of the rate of metabolism. A comparison of the three species in the rate of conversion to norchlorcyclizine showed that measurable amounts of norchlorcyclizine were present in rat blood 24 hours after the initial dose whereas this metabolite was undetectable in either pig or monkey blood at a similar time period. A comparision of chlorcyclizine metabolism showed that there was more rapid demethylation in monkeys than in pigs as indicated by the fact that chlorcyclizine became undetectable in the blood of monkeys ten days before it did in that of a pig.
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