Pulmonary delivery alters the disposition of raloxifene in rats

Abstract

Objective: Pulmonary delivery is an effective way to improve the bioavailability of drugs with extensive metabolism. This research was designed to study the different pharmacokinetic behaviours of small molecule drug after pulmonary delivery and intragastric (i.g) administration. Methods: Raloxifene, a selective estrogen receptor modulator with low oral bioavailability (~2%), was chosen as the model drug. Studies were conducted systematically in rats, including plasma pharmacokinetics, excretion, tissue distribution and metabolism. Key findings: Results showed that raloxifene solution dosed by intratracheal (i.t) administration exhibited relatively quick plasma elimination (t1/2 = 1.78 ± 0.14 h) and undetected absorption process, which was similar with intravenous injection. Compared with i.g administration, the bioavailability increased by 58 times, but the major route of excretion remained faecal excretion. Drug concentration on the bone and the target efficiency were improved by 49.6 times and five times, respectively. Benefited from quick elimination in the lung, chronic toxicity might be ignored. Conclusions: Pulmonary administration improved the bioavailability of raloxifene and further increased the distribution on the target organ (bone), with no obvious impact on its excretory pattern.