Kinetics of propylene glycol elimination and metabolism in rat.

The kinetics of 1,2-propanediol (PD) metabolism in vivo have been determined by employing the Michaelis-Menten rate equation; it was found that maximum metabolizing capacity was 8.33 mmole PD/kg/hr in the rat, which is equivalent to 1.06 kg/day for an average 70-kg human. The rate equation could be suitably used for optimizing the dosage schedule of a drug from the linear elimination pattern; in the present case this gave a Km value of 17.86 mmole/kg on the basis of the elimination rate of PD. The competitive inhibition of PD elimination by preadministration of pyrazole (Ki = 44 mumole/kg) demonstrated that the first step of the biotransformation of PD catalyzed by the NAD-dependent dehydrogenase might be the rate-limiting step for its in vivo metabolism. The low threshold level of the compound and significant rate of metabolism suggested that the CNS toxicity reported in clinical studies might be due to some of its metabolites such as lactaldehyde and other oxo compounds. Thus, PD could not be considered as an inert and innocuous substance.