Circadian Rhythm in Duration of Salicylate Excretion Referred To Phase of Excretory Rhythms and Routine. ∗

Summary

The duration of urinary salicy-late excretion following oral administration of the drug was studied on 6 human subjects standardized on a routine of sleep daily from 23:00 to 07:00. The drug was administered to each of the 6 subjects at 4 different time points, i.e., at 07:00, 11:00, 19:00 or 23:00 (4 separate tests at least 1 week apart). Average duration of drug excretion depended on the time of its administration. A circadian rhythm in this pharmacologic phenomenon was detected and analyzed by the so-called cosinor method and such results agreed with impressions gained from a conventional time plot of the data. By cosinor, duration of salicylate excretion was found to be longest when the drug was administered about 06:41. The 95% confidence arc of this circadian crest-phase estimate extends clockwise from 01:45 to 10:52. When expressed in degrees (with 360° = 24 hours), in relation to the middle of the daily span of rest and/or sleep, the crest ϕ of the rhythm in drug excretion occurs with a delay of 55° from this ϕ reference, the confidence arc of the crest extending clockwise from —341° to —118°. The pharmacologic rhythm here reported also is expressed in relation to the timing, in the same subjects, of 2 well-known excretory rhythms—in 17-OHCS and potassium excretion. The latter rhythms were determined on each subject in 2 separate 48-hour profiles and were also evaluated by the cosinor method, with excellent agreement of the ϕ and the C from one profile to the next.