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Prednisolone pharmacokinetics compared between night and day in asthmatic and normal subjects.

Prednisolone has proved to be an essential and even life saving drug in a number of medical conditions over the past twenty-five years. However its use remains largely empirical despite this long experience. One problem facing clinicians is whether to prescribe prednisolone once a day in the morning or evening, in divided doses or even on alternate days. There are good theoretical reasons for giving the drug once a day in the morning as this results in less pituitary adrenocortical suppression (Nichols, Nugent & Tyler, 1965; Siegre & Klaiber, 1966). Another factor affecting this choice would be the presence of a circadian rhythmicity in the disposition of prednisolone. There are reasons for suspecting that this might be the case as antipyrine and aminopyrine have been shown to exhibit a significant diurnal variation in half-life (Vesell, Shively & Passananti, 1977; Poley, Shively, Elliot & Vesell, 1978). Prednisolone has also been shown to exhibit a diurnal variation in binding to its carrier protein transcortin, the binding capacity is highest during the night (Angeli, Frajria, DePaoli, Fonzo & Ceresa, 1977). In this study we attempted to assess whether there is a significant diurnal variation in prednisolone pharmacokinetics. If this were so it might allow us to recommend its prescription at a particular time of day. Even though the effect on adrenal suppression would suggest an advantage in taking the drug in the morning, it could be that the circadian difference in pharmacokinetics might outweigh this if significant enough.