Pharmacodynamics of methylprednisolone phosphate after single intravenous administration to healthy volunteers

The pharmacokinetics and pharmacodynamics of methylprednisolone were investigated after intravenous administration of methylprednisolone phosphate to healthy subjects at seven different doses (16 to 1000 mg). Forty different pharmacodynamic parameters were followed for 1 week. The pharmacodynamic da...

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Bibliographic Details
Published in:Pharmaceutical research 1991-02, Vol.8 (2), p.263-268
Main Authors: DERENDORF, H, MOÊLLMANN, H, KRIEG, M, TUNN, S, MOÊLLMANN, C, BARTH, J, ROÊTHIG, H.-J
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biological and medical sciences
Blood Glucose - analysis
Bones, joints and connective tissue. Antiinflammatory agents
Dose-Response Relationship, Drug
Humans
Lymphocytes - drug effects
Male
Medical sciences
Methylprednisolone - pharmacokinetics
Methylprednisolone - pharmacology
Pharmacology. Drug treatments
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Summary:The pharmacokinetics and pharmacodynamics of methylprednisolone were investigated after intravenous administration of methylprednisolone phosphate to healthy subjects at seven different doses (16 to 1000 mg). Forty different pharmacodynamic parameters were followed for 1 week. The pharmacodynamic data were analyzed as a function of time as well as cumulative effects in form of the areas under the effect-time curves. Statistically significant dose-dependent effects of methylprednisolone were observed for 15 pharmacodynamic parameters. Highly significant (P less than or equal to 0.0001) effects were increases in glucose levels, number of white blood cells, and segmented granulocytes as well as a decrease in the number of lymphocytes. For these pharmacodynamic effects an integrated pharmacokinetic/pharmacodynamic model was derived that translates the methylprednisolone plasma concentration-time profiles into effect-time profiles. This model allows prediction of pharmacodynamic effects for any single dose in the range studied at any time point.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1015864709082