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Ibuprofen reduced human plasma melatonin (MT) after 2 h when administered orally (400 mg) at 2400 h. Increasing plasma concentrations correlated well with increasing inhibition of serum MT levels during this time. Maximum plasma ibuprofen coincided with minimum plasma MT in 3 out of 4 volunteers. Although two volunteers exhibited a partial recovery in MT levels, concentrations after 6 h were significantly less than 0600 h values in drug-free volunteers. Administration of ibuprofen (400 mg) at 1800 h delayed the nocturnal surge of plasma MT. When a slow release preparation of indomethacin (75 mg) was administered at 1800 h, the dark phase rise of plasma MT was completely prevented. Thus the longer acting cyclooxygenase inhibitor exhibited a longer lasting inhibition of plasma MT concentration.

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