Plasma Concentration and Tissue Distribution of Single Nose-only Exposure to 1,2-Propylene Glycol in Rat

OBJECTIVE To study the plasma concentration and tissue distribution of 1,2-propylene glycol(PG) by single nose-only exposure in rats, and to provide a reference for its safe application as an excipient in nasal drug delivery formulations.

METHODS Wistar rats were divided into 3 groups with male and female equally. PG was inhaled at doses of 100, 500, 1500 mg·kg⁻¹(target concentration of PG aerosol was 29.8 mg·L⁻¹, and the exposure time were 6, 26, 77 min, respectively). Plasma concentrations of PG were measured by blood sampling from 6 rats(half of each sex) in each group at different time points, and tissue concentrations of PG were measured by tissue sampling from 24 rats(half of each sex) in each group at different time points.

RESULTS The plasma concentration of PG increased rapidly in different dose groups after adminstration, with the peak time from the end of the administration to 30 min after the end of the administration. PG was mostly metabolized at 240 min after the end of the administration in the low dose group, and was mostly metabolized at 480 min in the medium and high dose groups. PG was metabolized in almost all rats 1440 min after the end of the administration. The AUC_(0-t) increased with increasing dose. The peak time in tissues was the end of administration. The concentration of PG in liver was lower than that of kidney and lung in the middle dose group, and there were no significant differences among tissues at the remaining groups, which were more evenly distributed.

CONCLUSION PG is rapidly absorbed by nose-only exposure in rats with peak time from the end of administration to 30 min after the end of administration, and was rapidly metabolized. PG is more evenly distributed in tissues. This study provides an experimental reference for the safety of the application of PG as an excipient in nasal drug delivery formulations.