Intranasal absorption of melatonin in vivo bioavailability study

The bioavailability of melatonin in rabbits after nasal administration of two formulations has been studied. In each case, a total amount of 1.5 mg melatonin in 50 mu l was administered and compared with 1.5 mg i.v. The test solutions were formulated with 40% polyethylene glycol 300 (PEG 300), one with 1% sodium glycocholate (+GC) and one without (-GC). The bioavailability for +GC was 94% (S.D. +/- 29%, n = 4), whereas the bioavailability for -GC was 55% (S.D. +/- 17%, n = 6). These results indicate that GC has an enhancer effect (P < 0.05). However, the relatively high bioavailability without GC shows that it might not be necessary to use an enhancer for a clinical relevant formulation. The pharmacokinetics of melatonin could be described by a one-compartment model, and the serum half-life was about 13 min. The absorption rate for both formulations was very fast (t(max) = 5 min) and C-max mean was 493 +/- 290 ng/ml (n = 4) and 249 +/- 125 ng/ml (n = 6) for +GC and -GC, respectively. (C) 1999 Elsevier Science B.V. All rights reserved.