A melatonin preparation with a pulsatile liberation pattern: a new form of melatonin in replacement therapy

Using melatonin (MLT) as a circadian synchroniser in humans to treat rhythm disorders, it is desirable to have controlled-release dosage forms. Following in vitro liberation tests, one fast-release form containing 5 mg MLT (capsule A) and two oral pulsatile-dosage forms containing 10 mg MLT each (capsules B and C) were studied in a randomised, single-dose, threefold cross-over study in 15 healthy male volunteers after investigation of capsule B in dogs. Mean peak concentrations of MLT in serum (pmol/ml) were reached between 0.5 h and 0.75 h: Cmax1 20.7 (A), 16.4 (B), 9.7 (C). Capsules B and C released a second MLT pulse after about 3.5 h with Cmax2 of 13.0 and 17.5 pmol/ml, respectively. The time course of the renally excreted main metabolite 6-sulphatoxymelatonin (aMT6s) correlates with that of changes in MLT serum concentrations. The kinetic profile of the delivery system is adjusted to the pattern of sleep maintenance disturbances.