Pharmacokinetics and pharmacodynamics of prednisolone after intravenous and oral administration.
The pharmacokinetics and pharmacodynamics of prednisolone were investigated according to four different routes of administration: 20 and 40 mg prednisolone orally in the morning, 20 mg prednisolone orally in the evening and 40 mg prednisolone intravenously in form of prednisolone phosphate in the morning. The plasma levels of prednisolone were followed using HPLC. To study the pharmacodynamics of prednisolone, glucose levels and various blood cell parameters such as erythrocytes, leukocytes, segmented neutrophilic granulocytes, eosinophils, basophils, monocytes and lymphocytes were followed. To summarize the data, the area under the effect-time-curve (AUCE) was calculated by the trapezoidal rule. The results show that the pharmacokinetics of prednisolone is dose-dependent (non-linear) and time-dependent. Prednisolone concentrations in plasma after a 20 mg and 40 mg dose are very similar, indicating that the pharmacokinetics of prednisolone are non-linear and dose-dependent with a higher clearance for higher concentrations. The comparison of 20 mg administered in the morning with the same dose given in the evening shows that the pharmacokinetics of prednisolone after oral administration of equal doses changes during the day with higher concentrations in the morning than in the evening. Furthermore, the results of the present study confirm the presence of pharmacodynamic corticosteroid effects on blood cell count and blood glucose. No statistically significant differences were observed for the four different treatments. In summary, it can be concluded that due to the complex pharmacokinetics of prednisolone, it is difficult to make accurate predictions of the expected effect-time relationships.
Barth
J
J
Universitätsklinik Bergmannsheil, Bochum, Germany.
Damoiseaux
M
M
Möllmann
H
H
Brandis
K H
KH
Hochhaus
G
G
Derendorf
H
H
D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D011239:Prednisolone