CIRCADIAN RHYTHM AND ITS SIGNIFICANCE

.. . Of Urinary pH with and Wnhout Chronic Antacid Use In a S-day, 3·treatment, cross-Qvcr study in 24 bea1tby male adult volunteers a single 20ml dose. of antacid (,Maalox'; a magnesium and aluminium suspension) had little effect on urinary pH (I]. Du(ing ~hro~c antacid therapy with 'Maalox' qid for 4 days, the shapeofthecircadian urinan' pH curve remained unaltered. However, theentire curve was shifted into a more alkaline . direction, based on the evaluation of 1562 separate urine samples collected over 5-hour intervals by day and a 9-hour interval at night. There was a significam correlation ooefficjem of O. 946 (p < 0.00 I), between the decreaseJn urinary hydrogen ion coooentration caused by chronic administration of 'Maalox' suspension and the initial urinary hydrogen ion concentration during a control period. The maximum effect of chronic antacid treatment occurred on the 3rd day of the test. Urinary hydrogen ion coruntratioD returned to control values within 12 bour.; after stopping 'MaaJox'. It is recommended that:

• the efTect of antacid on the circadian rhythm of urinary pH be considered in designing trials involving drug-drug interactions with antacids .

• pH values should not be averaged as usually reported in the literature. but should be converted to hydrogen ion concentrations before statistical analysis .

. , . And Affecting Drug Metabolism Temporal variations in antipyrine salivary half- life were studied in 19 healthy volunteers after a single 18mg/ kg dose given at 7:00am. (21 Saliva specimens were obtained at balf-hour intervals from I 0:30am to 2:00pm and from I 0:30pm to 2:00am .. There were no significant group mean differences between the antipyrine half·lives calculated using the noon period and those calculated using the midnight period saliva sampleS, or usini the whole 24-hour period. Neither did mean metabolic clearance rates or mean apparent volum.es of distributiO.D differ among these.periods. However, 12 of the 19 subjects showed a Change of more than 10 % in amipyrine half·life between the noon and midnight periods, 7 subjects showing increases and 5 decreases in half-life'at the midnight peljod.1herangeofextremes was from an increase in half-life of 113 % to a decrease'of42 %. Repeated studies in S subjects showed that these results were reproducible with respect to dirtction and magnitude of change. Neither the direction nor magnitude of the temporal variation was altered if the antipyrine dose was given, at 1 :OOpm instead of 7:00am. This study 'supports the concept that an endogenous circadian rhythm affects drug metabGIism.'

[I} AyrtS. J .W. et~.: EuropeanJoumai ofClinic:al Pharmacoloe,y 12: 41 SINo 6. 1971) (2[ Vesell. E.s. et aI .: ain~ Pharmacology a-:<d Therapeutic'; 22: 843(Oec 1917)

INPHARMA 2811\ JIlIlUBfY, 1978 pIe