Aspects of chronopharmacokinetics and chronergy of ethanol in healthy man.

Eight health subjects (3 males and 5 females) aged 20-25 years ingested ethanol once weekly at one of 6 different timepoints (0100, 0500, 0900, 1300, 1700, 2100) arranged in random order over 6 successive weeks. On a seventh week ethanol was ingested again at 1300. At each time point each subject, who had taken a standard meal 5 h previously and fasted thereafter, received a dose of 0.8 g of ethanol/kg body weight, taken orally within 2 min. Subsequently subjects emptied their bladders collecting all the urine at regular intervals. Two days later a matched control was performed in which an equal volume of water replaced ethanol ingestion. The rate of removal of ethanol from the body was estimated by a linear least-squares regression of the urine concentrations of ethanol in 5 samples obtained from 120 to 300 min post-ingestion. Group cosinor analysis showed significant circadian rhythms of ethanol removal rates in both the male and female subjects, with acrophases at 0757 and 0244 respectively. Ingestion of ethanol produced a diuresis which lasted about 100 min. The magnitude of this diuresis was dependent upon the time of ethanol ingestion. A significant rhythm of diuresis, assessed as the volume of urine produced in the first 100 min following ethanol ingestion in excess of the produced in the same period in the matched control, was detected with acrophase at 0800-0900. Both the amount and circadian rhythm of diuresis were due to changes in free water excretion.