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 microl 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 (tmax=5 min) and Cmax mean was 493+/-290 ng/ml (n=4) and 249+/-125 ng/ml (n=6) for +GC and -GC, respectively.
Bechgaard
E
E
The Royal Danish School of Pharmacy, Department of Pharmaceutics, Universitetsparken 2, DK-2100, Copenhagen O, Denmark.
Lindhardt
K
K
Martinsen
L
L
D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001825:Body Fluid Compartments; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000378:metabolism; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits
D000975:Antioxidants; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D008550:Melatonin