Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 am versus 4 pm.

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 methylprednisolone 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.

RCT Entities:   Population Interventions Outcomes