Prednisolone concentrations in cerebrospinal fluid after different prednisolone prodrugs.

Abstract

The concentration‐time curves of prednisolone in cerebrospinal fluid (CSF) and plasma were measured following an equimolar i.v. bolus dose of prednisolone phosphate (five patients) and prednisolone phthalate (four patients). Independent of the prodrug administered, the value of the AUC (0.360 min) in CSF was more than three times lower than the corresponding value in plasma. The AUCs of unbound prednisolone in plasma were higher after prednisolone phosphate, than after prednisolone phthalate (68.1 +/− 15.7 vs 19.0 +/− 5.2 micrograms ml‐1 min, P less than 0.001). Similarly, the AUCs of prednisolone were higher in the CSF after prednisolone phosphate, than after prednisolone phthalate (17.6 +/− 2.8 vs 3.3 +/− 1.0 micrograms ml‐1 min, P less than 0.0001). The results indicate that the concentrations of prednisolone in CSF are much lower than the unbound concentrations in plasma and that therapeutic inequivalence should be expected when the two prodrugs are given in equimolar doses.

Sudden Sensorineural Hearing Loss

“…Therefore, at the beginning of our treatment of SSNHL and according to the principles of high-dose (pulse-dose) corticoid therapy used by other specialties (neurology, transplantation medicine, etc), we applied similar high doses. Bü hrer et al 31 demonstrated in humans that after intravenous administration of prednisolone, the concentration in cerebrospinal fluid was only approximately one third of the corresponding plasma concentration. One hour after intravenous application of methylprednisolone in the perilymph of guinea pigs, Parnes et al 32 measured only one sixth of the concentration of the corresponding plasma level.…”

A practical approach for evaluating population and individual bioequivalence

“…Additional references were provided by a search conducted by the Clinical Literature Information department at Merck Research Laboratories that covered a number of other databases besides MEDLINE. The di culties that were reported occurred for drugs with narrow therapeutic windows [29][30][31][32] or for substitutions that were not even 'average' bioequivalent to the original product [33][34][35][36][37]. Imposition of stricter requirements for bioequivalence materially decreased the incidence of reported di culties [28].…”

Der Einfluss von Glukokortikoiden bei der Therapie des Hörsturzes

“…ähnlich hohe Dosen (1000 mg/die) appliziert. Bührer et al [30] Neuere Studien haben jedoch gezeigt, dass mit etwa 300 mg Prednisolon alle Kortikoidrezeptoren des Kör-pers besetzt sind [32].…”