Prednisolone pharmacokinetics compared between night and day in asthmatic and normal subjects [letter]

Mcallister, W. A. C.; Mitchell, D.; Collins, J. V.

doi:10.1111/j.1365-2125.1981.tb00538.x

Cited by 23 publications

(9 citation statements)

References 9 publications

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“…An important question still awaiting an answer is whether changes in effectiveness are related either to the chronokinetics of corticosteroids or to the chronesthesy of the target organs for these active agents, or to both. McAllister et al (1981) studied the disposition of plasma prednisolone in six healthy male subjects (acute administration; 20 mg/24 hr; Rx at 0800 and 2000 on different experimental days scheduled at least 1 week apart) and in five chronic stable asthmatics who had been treated previously with prednisolone daily for at least 6 months. No significant differences were found between the nighttime and daytime studies for any of the pharmacokinetic data (half-life, Cmax , T max, AUC, etc.…”

Section: Corticosteroid Chronopharmacokineticsmentioning

confidence: 99%

“…With respect to this, the validity of McAllister's (1981) conclusion regarding the absence of chronopharmacokinetics for plasma prednisolone must be questioned since only two time points (0800 and 2000) were investigated. Again, it is possible that prednisolone fails to exhibit chronokinetics, but to be certain additional times of study, selected for pertinence with regard to both the synchronization schedule and biological temporal structure, are necessary.…”

Section: Effects Of Meal Timingmentioning

confidence: 99%

See 1 more Smart Citation

Biological Rhythms and Medicine

Reinberg¹,

Smolensky²

1983

Topics in Environmental Physiology and Medicine

151

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Section: Corticosteroid Chronopharmacokineticsmentioning

confidence: 99%

Section: Effects Of Meal Timingmentioning

confidence: 99%

Biological Rhythms and Medicine

Reinberg¹,

Smolensky²

1983

Topics in Environmental Physiology and Medicine

151

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“…The reported circadian variation in prednisolone serum binding (Angeli et al, 1978) has led to speculation regarding circadian variation in prednisolone disposition (Pickup, 1979;McAllister et al, 1981a). Because during continuous therapy, the free concentration of a drug in plasma is determined only by dose rate and free clearance, changes in plasma protein binding will not alter the concentration of physiologically active unbound prednisolone.…”

Section: Time Ofadministrationmentioning

confidence: 99%

“…This report led to the suggestion that circadian variations in cortisol concentrations might produce alterations in prednisolone disposition (Pickup, 1979), but no changes in area under the total prednisolone plasma concentration-time curve were found after oral doses of approximately 0.3 mg/kg given at 08.00 h and 20.00 h (McAllister et al, 1981a). The above authors speculated that circadian alterations in prednisolone disposition might be observed if unbound, rather than total, *Correspondence to: Dr P. J.…”

Section: Introductionmentioning

confidence: 99%

Alterations in prednisolone disposition as a result of time of administration, gender and dose.

Meffin¹,

Brooks²,

Sallustio³

1984

Brit J Clinical Pharma

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1 The disposition of total and free prednisolone has been studied in four male and four female volunteers, each of whom received an intravenous dose of 0.075 mg/kg (low) and 1.5 mg/kg (high) of prednisolone at both 06.00 h and 18.00 h. 2 For the low dose, free prednisolone clearance was 14% lower (P = 0.012) and time-averaged prednisolone free fraction was 22% higher (P < 0.001) in the morning, there being no circadian difference in total prednisolone clearance. There was no circadian differences in prednisolone disposition at the high dose. These findings are consistent with a mechanism in which cortisol causes a simultaneous competitive inhibition of prednisolone clearance and plasma protein binding at low, but not at high prednisolone doses. 3 Prednisolone clearance was higher in female than in male subjects, the mean increase being 18% (P = 0.022) for total prednisolone and 21% (P = 0.036) for free prednisolone. 4 Mean total prednisolone clearance and steady-state distribution volume were two-fold higher at the high vs the low dose (P < 0.001), but free prednisolone clearance showed a dose dependent decrease of 11% (P = 0.019). There was no change in free prednisolone steady-state distribution volume.

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“…This process is illustrated in Fig. 2, and may be described by the following: (7) in which C is the cortisol concentration at time t, C o , is the initial cortisol concentration, and C Mp , is the methylprednisolone concentration as described by the following: (8) In contrast to the basophii model, the cortisol model requires an instantaneous input function for C MP necessitating the use of the monocxponential fitting. By use of the PCNONLIN computer program, the cortisol data for alt three phases were simultaneously fitted to equations 5, 6, and 7, and the fitted parameters Rm, Rb, tz, k c (8 AM), k c (4 PM), IC 50 (8 AM), IC 50 (4 PM), C o (8 AM), and C o (4 PM) were obtained.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM

Fisher

Ludwig

Wald

et al. 1992

Clin Pharmacol Ther

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The temporal variations in the pharmacokinetics and pharmacodynamics of methylprednisolone at 8 AM versus 4 PM were investigated in six healthy male volunteers. Subjects completed three phases: no drug administration, 20 mg intravenous methylprednisolone at 8 AM, and the same dose at 4 PM. Methylprednisolone clearance was 28% greater in the afternoon. The suppressive effects of methylprednisolone on basophils (measured as whole blood histamine), helper T lymphocytes, and cortisol concentrations, assessed by the ratio of the area under the curve (AUC) after methylprednisolone to the baseline AUC, were not different between the phases. The 50% inhibitory concentration values for methylprednisolone derived from pharmacodynamic models were also similar, indicating no difference in intrinsic responsiveness. However, cortisol concentrations returned to baseline about 4 hours earlier after the 4 PM compared with the 8 AM dose because of the enhanced afternoon methylprednisolonc clearance. These findings are in agreement with other studies that suggest adequate clinical effects and less disturbance of cortisol circadian behavior when methylprednisolone is administered as a single dose in the morning.Corticosteroids are an important class of therapeutic agents because of their antiinflammatory and immuno-suppressive properties. Ideal dosing regimens have yet to be elucidated for the treatment of numerous disease states. Currently, corticosteroids are most often administered as a single morning dose. However, these agents may be administered as divided doses or even as a single evening dose in those conditions requiring adrenal suppression. 1 Numerous drugs, including theophylline, 2 phenyloin, 3 and cisplatin, 4 have demonstrated temporal variations in their pharmacokinetics. This is not surprising because it has been shown in animals that both hepatic drug-metabolizing activities and renal clearance (CL R ) mechanisms exhibit circadian variations. 5,6 Human chronopharmacokinetic studies with exogenous corticosteroids are limited. Prednisolone has been evaluated in three studies with conflicting findings. The first study 7 found no circadian differences in prednisolone Copyright © 1992 clearance, volume of distribution (V), or half-life (t ½ ). The second study 8 found circadian differences in the clearance (CL) of free prednisolone and the free fraction when it was given as a low dose. The third study 9 found circadian variation in all parameters investigated. To date, no human chronopharmacokinetic study with methylprednisolone has been reported. In male Norwegian rats, the maximum methylprednisolone t ½ was noted to occur when the drug was administered at 6 PM, the commencement of the nocturnal activity period of the animals, whereas the shortest t ½ was documented with noon administration, or midway through the diurnal rest span. 10 The pharmacodynamics of exogenous corticosteroids may show temporal variations. The susceptibility of the hypothalamic-pituitary-adrenal axis to suppression in humans, as measured...

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Prednisolone pharmacokinetics compared between night and day in asthmatic and normal subjects [letter]

Cited by 23 publications

References 9 publications

Biological Rhythms and Medicine

Biological Rhythms and Medicine

Alterations in prednisolone disposition as a result of time of administration, gender and dose.

Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM

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