CIRCADIAN CHANGES IN INHIBITORY EFFECTS OF AN ANTIHISTAMINIC DRUG IN MAN

[摘要] Six apparently healthy subjects were standardized for one week on a routine of diurnal activity and nocturnal (23[degree][degree]-07[degree][degree]) rest. During three different 24-hr, spans, 2 functions were studied at 4-hr, intervals on each subject, I.e., the areas of erythema and wheal, evaluated at 15 to 20 min. after the intradermal injection of 10 [mu]g of histamine (flexor surfaces of the forearms). For each subject, a control curve was 1st obtained on the circadian variation of skin reactions to histamine[long dash]in the absence of any antihistaminic drug administration. A 2nd and a 3rd group of profiles was obtained after a single (4 mg) dose of oral Periactine, an antihistaminic drug. Periactine was taken at 07[degree][degree] for one of these last profiles and at 19[degree][degree] for the other one. The changes in responses after Periactine administration were expressed as a percentage deviation from the control responses. The antihistaminic effect of Periactine administered at 07[degree][degree] lasted for 15 to 17 hr. This inhibitory effect lasted only 6 to 8 hr. when the drug was taken at 19[degree][degree]. The duration of this drug activity depends upon the timing of its administration, in keeping with F. Halberg''s concept of the hours of changing responsiveness.