The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study

BACKGROUND: We formulated mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers. METHODS: Mianserin suppositories were prepared by a melting technique using Tetramide® tablets and Witepsol H-15 as the suppository base. Pharmacokinetics of this 30-mg mianserin preparation were evaluated in three beagle dogs and three healthy adult males, in line with ethics committee approval. Plasma mianserin levels were determined using gas chromatography–mass spectrometry. RESULTS: In dogs, the maximum plasma mianserin concentration (C(max)) was 1.3 ± 0.4 ng/mL, the time to C(max) (t(max)) was 5.5 ± 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC(0-24)) was 18.9 ± 1.9 h・ng/mL. In humans, the C(max) was 14.6 ± 6.3 ng/mL, the t(max) was 8 h, and the AUC(0-24) was 266 ± 103 h・ng/mL. CONCLUSIONS: The current study characterized the pharmacokinetics of mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower C(max) and a delayed t(max), although AUC(0-24) values were comparable. It will be necessary to identify an appropriate dose that produces an adequate plasma mianserin concentration for effective and safe clinical use. TRIAL REGISTRATION: UMIN000013853.