Pharmacokinetics of Propylene Glycol in humans During Multiple Dosing Regimens

Introduction:
This text is a pharmacokinetic study on propylene glycol in humans during multiple oral-dosing regimens. The study investigates the accumulation and intersubject variability in clearance of propylene glycol in humans. The results of this study are relevant for assessing the safety and efficacy of drugs that use propylene glycol as a solvent vehicle.

Key Points:

* Propylene glycol is rapidly absorbed and has a terminal elimination half-life of approximately 4 hours.
* after a minimum of 10 half-lives of maintenance dosing, the accumulation of propylene glycol differed significantly among individuals due to variability in apparent clearance.
* The average apparent total body clearance is 0.1 L kg . h and may be concentration dependent.
* The apparent volume of distribution is 0.5 L kg, approximating total body water.
* Propylene glycol is metabolized to carbon dioxide and water through metabolic intermediates and is also excreted unchanged via the renal pathway.
* The study reports cases of propylene glycol toxicity in humans during chronic ingestion, including two children who experienced symptoms such as stupor, tachypnea, tachycardia, and diaphoresis after receiving propylene glycol as a solvent for vitamin preparations.
* The pharmacokinetics of propylene glycol in humans has not been well described, and the present study aimed to investigate its pharmacokinetic behavior during multiple-dosing regimens.

Main Message:
The study highlights the potential for propylene glycol toxicity in humans during chronic ingestion, particularly in vulnerable populations such as children. The variability in apparent clearance and the accumulation of propylene glycol in humans during multiple dosing regimens suggest that the use of propylene glycol as a solvent in long-term drug therapy needs to be further evaluated. as an expert in regulatory matters, it is crucial to consider these findings when assessing the safety and efficacy of drugs that use propylene glycol as a solvent vehicle.

Yu, Dale K., William F. Elmquist, and Ronald J. Sawchuk. “Pharmacokinetics of Propylene Glycol in humans During Multiple Dosing Regimens.” Journal of Pharmaceutical Sciences 74, no. 8 (august 1985): 876–79. https://doi.org/10.1002/jps.2600740815.