Pharmacokinetics of propylene glycol in the rabbit

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Abstract
Propylene glycol (PG) is widely used as a drug solvent in the pharmaceutical industry. However, it has produced central nervous system toxicity during chronic administration. The current study was undertaken to describe the pharmacokinetics of propylene glycol during acute and constant-rate intravenous dosing, using the rabbit as an animal model. In the acute dosing experiment, metabolism of PG was the dominant disposition pathway, characterized by concentration-dependent metabolic clearance. Renal excretion of PG accounted for only 2.4 to 14.2% of the total dose following acute administration due to significant reabsorption in the rabbit kidney. An ascending-convex relationship exists between renal clearance and urine flow. During constant-rate intravenous infusion studies, there was a disproportionate relationship between infusion rate and steady-state concentration, providing further evidence for capacity-limited disposition kinetics. The ascending-convex relationship between renal clearance and urine flow was also apparent in the long-term infusion studies.