Summary
Introduction:
This text is a scientific journal article that describes a study on the pharmacokinetics of propylene glycol in rabbits. The study was conducted to characterize the absorption, distribution, metabolism, and excretion of propylene glycol in rabbits during both acute and chronic intravenous dosing. The study's findings provide valuable insights into the disposition and elimination of propylene glycol in rabbits and have implications for its use as a solvent in pharmaceutical formulations.
Key Points:
* Propylene glycol is a widely used solvent in pharmaceutical formulations.
* The study used a 3 x 3 randomized complete block design with nine New Zealand White male rabbits.
* acute intravenous doses of propylene glycol (0.5 g/kg, 1.0 g/kg, and 2.0 g/kg) were administered to the rabbits.
* Blood and urine samples were collected up to 8 or 12 hours after dosing.
* Chronic intravenous dosing regimens were also studied, with propylene glycol infused intravenously at two infusion rates for 51 or 52 hours.
* Plasma and urine propylene glycol levels were determined using a gas-liquid chromatographic procedure.
* The study found that metabolism of propylene glycol was the dominant disposition pathway, and renal excretion accounted for only 2.4 to 14.2% of the total dose.
* There was a disproportionate relationship between infusion rate and steady-state concentration, indicating capacity-limited disposition kinetics.
* an ascending-convex relationship was observed between renal clearance and urine flow during both acute and chronic dosing.
Main Message:
The study provides valuable information on the pharmacokinetics of propylene glycol in rabbits, which is important given its widespread use as a solvent in pharmaceutical formulations. The findings suggest that the metabolism of propylene glycol is the dominant disposition pathway, and renal excretion is limited due to significant reabsorption in the rabbit kidney. The ascending-convex relationship between renal clearance and urine flow indicates that renal clearance is dependent on urine flow. The disproportionate relationship between infusion rate and steady-state concentration suggests capacity-limited disposition kinetics. These findings have implications for the safe use of propylene glycol in pharmaceutical formulations, particularly in patients with impaired renal function or hepatic dysfunction.
Citation
Yu, Dale K., and Ronald J. Sawchuk. “Pharmacokinetics of Propylene Glycol in the Rabbit.” Journal of Pharmacokinetics and Biopharmaceutics 15, no. 5 (October 1987): 453–71. https://doi.org/10.1007/BF01061757.
