Clinical Investigation

Kidney International (1982) 21, 621–626; doi:10.1038/ki.1982.69

Prednisone and prednisolone bioavailability in renal transplant patients

John G Gambertoglio1, Felix J Frey1, Nicholas H G Holford1, Jytte L Birnbaum1, Patricia Stanik Lizak1, Flavio Vincenti1, Nicholas J Feduska1, Oscar Salvatierra Jr1 and William J C Amend Jr1

1Departments of Pharmacy, Medicine, and Surgery, University of California, San Francisco, California

Correspondence: Dr J G Gambertoglio, Department of Pharmacy, University of California, San Francisco, California 94143, USA

Received 1 June 1981; Revised 21 September 1981.

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Abstract

Prednisone and prednisolone bioavailability in renal transplant patients. Prednisone and prednisolone are drugs with the potential for therapeutic inequivalence due to bioavailability problems. The objective of our study was to compare the systemic bioavailability of prednisolone from oral prednisone and prednisolone. Nine kidney transplant patients receiving prednisone (12.5 to 22.5 mg per day) were administered, in a randomized fashion, the same dose of oral prednisone (Deltasone®), oral prednisolone (Delta-cortef®) and intravenous prednisolone (Hydeltrasol®). Prednisolone and prednisone levels were measured using a specific high-pressure liquid chromatographic assay. Since prednisolone exhibits dose-dependent pharmacokinetics because of nonlinear plasma protein binding, bioavailability was determined from unbound as well as total drug concentrations. Mean prednisolone bioavailability from oral prednisone and oral prednisolone, compared to the intravenous dose, was 84.5 plusminus 17.8% and 95.5 plusminus 17.6% using unbound drug concentrations and 86.1 plusminus 9.1% and 93.6 plusminus 9.2% determined from total drug concentrations. These differences were not statistically significant. Furthermore, no significant differences were observed between the two oral formulations in peak prednisolone levels, time of peak levels or half-life using either total or unbound drug concentrations. The results from our study indicate that both of the oral preparations tested provide similar bioavailability of active prednisolone and the conversion of prednisone to prednisolone occurs rapidly.

Biodisponibilité de la prednisone et de la prednisolone chez des transplantes renaux. La prednisone et la prednisolone sont des médicaments dont le potentiel thérapeutique peut différer en raison de problèmes de biodisponibilité. Le but de notre étude a été de comparer la biodisponibilité systémique de la prednisolone à partir de prednisone ou de prednisolone données per os. Neuf transplantés rénaux recevant de la prednisone (12,5 à 22,5 mg/jour) ont reçu de façon randomisée la même dose de prednisone (Deltasone®) orale, de prednisolone (Deltacortef®) orale ou de prednisolone (Hydeltrasol®) intraveineuse. Les concentrations de prednisolone et de prednisone ont été déterminées avec un dosage spécifique utilisant une chromatographic liquide à haute pression. La prednisolone ayant une pharmacocinétique dose-dépendante en raison de la non linéarité de sa liaison aux protéines plasmatiques, sa biodisponibilité a été déterminée à partir de ses concentrations plasmatiques totale et libre. La biodisponibilité moyenne de la prednisolone à partir de prednisone ou de prednisolone orale, comparée à l'administration intraveineuse était de 84,5 plusminus 17,8% et 95,5 plusminus 17,6% à partir des concentrations libres et de 86,1 plusminus 9,1% et 93,6 plusminus 9,2% à partir des concentrations totales. Ces différences n'étaient pas significatives. De plus, il n'y avait pas de différences significatives entre les 2 préparations orales en ce qui concerne les pics de concentrations de prednisolone, l'heure de ces pics de concentrations ou la demi-vie, qu'on utilise les concentrations totales ou libres. Les résultats de notre étude indiquent que les deux préparations orales testées offrent une biodisponibilité de prednisolone active identique, et que la transformation de prednisone en prednisolone se produit rapidement.

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