[Pharmacokinetics and pharmacodynamics of prednisolone following extremely high dosage as prednisolone hemisuccinate].

Plasma levels of prednisolone and prednisolone hemisuccinate of volunteers were measured with HPLC following i.v. injections of 1200 and 75 mg of prednisolone, given as the water-soluble hemisuccinate ester. The hemisuccinate ester is hydrolyzed relatively quickly with a plasma half-life between 18 and 25 min, and the resulting prednisolone has a plasma half-life of 3.5-3.7 h. The dose dependency of the pharmacokinetic parameters indicates a partial saturation of the metabolizing enzymes as consequence of the application of the high dose of prednisolone. In saliva no hemisuccinate could be detected. The prednisolone saliva concentration corresponds with those of non-protein-bound prednisolone in plasma measured at the same time. Only minor quantities of intact ester (1-8%) or intact prednisolone (2-4%) are excreted in urine. Following the application of 1200 mg prednisolone the endogenous cortisol level is partially suppressed only 24 h after the i.v. injection; 48 h later the difference from the basis value is not statistically significant. Leukocytosis and granulocytosis are at maximum 24 h after the injection of the high dose, and after 48 h normal values are observed. Lymphocytes and monocytes fall below normal levels for a longer time after 1200 mg compared to 75 mg, the minimum is between 4 and 8 h. Glucose levels are enhanced dose-dependently. They are normalized even after the extremely high dose at 24 h. Sodium, potassium, calcium, plasma proteins, urea, creatinine, hematocrit and hemoglobin showed no significant differences within 48 h following the injections.