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

Abstract

BackgroundWe formulated mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers.MethodsMianserin 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.ResultsIn dogs, the maximum plasma mianserin concentration (Cmax) was 1.3 ± 0.4 ng/mL, the time to Cmax (tmax) was 5.5 ± 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 18.9 ± 1.9 h・ng/mL. In humans, the Cmax was 14.6 ± 6.3 ng/mL, the tmax was 8 h, and the AUC0-24 was 266 ± 103 h・ng/mL.ConclusionsThe current study characterized the pharmacokinetics of mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower Cmax and a delayed tmax, although AUC0-24 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 registrationUMIN000013853.

Bioavailability of Drugs From Suppositories in Clinical Practice After 1995

“…At present, haloperidol injection is the only option available to treat delirium to patients who have difficulties with oral administration. The first-pass fraction of approximately 32% following oral administration of mianserin hydrochloride was observed in six healthy male subjects and it is maybe promising for its rectal delivery (23). Many drug classes, including antidepressants, have limited non-oral options, which makes it challenging to optimally manage neuropsychiatric conditions in patients without enteral access.…”