Pharmacokinetics of Transdermal Melatonin Products: A Randomized, Crossover Clinical Trial

Study Objectives In some countries, melatonin is sold without a prescription and dosage is unregulated. This includes transdermal products without specific quantities of melatonin listed on the label. Our aim was to compare the pharmacokinetics of melatonin administered in oral, lotion, and bath product forms in a randomized, crossover clinical trial. Methods Melatonin levels in transdermal products were measured via HPLC and fluorescence. To determine pharmacokinetics, three different treatments (oral tablets, lotion, and bath immersion) were administered to twelve undergraduate participants in a random order. Five additional participants completed bath product treatment only. Participants collected saliva samples up to 48 hours after administration, which were analyzed for melatonin by enzyme-linked immunosorbent assay. Results Melatonin lotion products displayed lot-to-lot variability as well as changes in formulation and product claims; the lot used for this clinical trial contained 1.3 ± 0.05 mg melatonin/g lotion. Oral (n=11) and lotion treatments (n=12) caused maximum salivary melatonin levels within 30 minutes after administration, but bath immersion did not cause increases in saliva melatonin (n=17). The half-life of oral melatonin was 1.17 [0.69 – 1.65] hours versus 5.72 [3.75 – 7.68] hours for lotion treatment (p = 0.011, effect size r = 0.770). Conclusions Melatonin lotions contain undisclosed potent doses, are absorbed quickly, and remain at high physiological levels into the following day. This study is registered on clinicaltrials.gov (NCT06382610) and was funded by the Sleep Research Society and the National Heart, Lung, and Blood Institute of the National Institutes of Health Award Number R15HL179371.