2018 Volume 44 Issue 3 Pages 136-140
Trazodone is an antidepressant having hypnotic and sedative effects. It has recently been applied for the treatment of insomnia in elderly patients and inpatients with delirium. Because the only commercially available dosage of trazodone is tablet form in Japan, trazodone is not applicable for patients who have difficulty taking oral medication; these patients are very common among the above patient population. Therefore, we attempted to develop rectal suppositories of trazodone to facilitate its administration in patients who cannot take medicines orally. The suppositories were prepared using Witepsol W-35 as the base. Trazodone tablets and prepared suppositories were administrated to 5 healthy adult volunteers, and the days of administration were separated by a one-week washout period. Serum concentration was measured using liquid chromatography tandem-mass spectrometry (LC-MS/MS). In oral administration, the maximum serum concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve from 0 to 8 h (AUC0→8) were 570.91 ± 129.49 ng/mL, 1 h, and 2,499.50 ± 546.19 h·ng/mL, respectively. In rectal administration, Cmax was not clear and serum concentration was almost sustained, AUC0→8 was 1,727.70 ± 435.25 h·ng/mL. Pharmacokinetic parameters revealed the sustained absorption of trazodone in suppository, absorption and serum drug concentrations after rectal administration were lower than those after oral administration, which might prevent adverse effects. The results of this study suggest that trazodone suppositories prepared using Witepsol as the base might be safely applicable and useful for patients who find it difficult to take oral medicine.
