A Comparison of the Pharmacokinetics of Oral and Sublingual Cyproheptadine

Abstract

Background: Cyproheptadine is reported to be effective in treating serotonin syndrome. It is only available as an oral preparation and administration after SSRI overdose treated with activated charcoal is problematic. Sublingual administration may circumvent this problem. The pharmacokinetics of sublingual cyproheptadine are not characterized. This study compares the pharmacokinetics of cyproheptadine following oral and sublingual administration. Methods: Cross‐over, non‐blinded, volunteer study using five healthy males. Eight milligrams of oral and sublingual cyproheptadine were administered on separate occasions with a one‐week washout period. Sublingual arm subjects were pretreated with 50 g of oral activated charcoal 30 min prior to cyproheptadine, to prevent any gut absorption. Serum cyproheptadine concentration was measured at baseline, 30 min, and 1, 2, 3, 4, 6, 8, and 10h by liquid chromatography and mass spectroscopy. Results: Mean Cmax for oral and sublingual were 30.0 µg/L and 4.0 µg/L respectively; mean Tmax were 4h and 9.6h; mean AUC were 209 and 25 µg.hr/L. Mean ± SEM within‐subject difference between oral and sublingual Cmax was 25.9 ± 4.1 (p = 0.003) and AUC was 184 ± 31 (p = 0.004). Conclusions: Serum concentrations after sublingual cyproheptadine are significantly less than after oral administration. At these concentrations, the sublingual route is unlikely to be effective in treating serotonin syndrome.

Keywords :

• Cyproheptadine
• Serotonin syndrome
• Pharmacokinetics
• Sublingual route