Artigo Revisado por pares

Pharmacokinetics of Methylprednisolone and Prednisolone After Single and Multiple Oral Administration

1997; Wiley; Volume: 37; Issue: 10 Linguagem: Inglês

10.1002/j.1552-4604.1997.tb04266.x

ISSN

1552-4604

Autores

Shashank Rohatagi, Jürgen Barth, H Möllmann, Günther Hochhaus, Andrea Soldner, Carsten Möllmann, Hartmut Derendorf,

Tópico(s)

Analytical Methods in Pharmaceuticals

Resumo

The pharmacokinetics of methylprednisolone and prednisolone were evaluated in 24 healthy men after oral administration of single and multiple doses for 3 days. For each drug, 6 different administration regimens with doses ranging from 1 to 80‐mg of methylprednisolone and 1.25 to 100‐mg of prednisolone, and administration intervals ranging from 3 to 24 hours for both were investigated. Plasma was assayed using a normal phase high‐performance liquid chromatography (HPLC) method. Methylprednisolone showed linear pharmacokinetics with no apparent dose or time dependency. Prednisolone showed marked dose dependency with higher clearance and volume of distribution for higher doses. This can be explained by its saturable protein binding of plasma, because unbound clearance and unbound volume of distribution were not dose‐dependent. After multiple administration, prednisolone showed significant time‐dependent pharmacokinetics with increased unbound clearance and increased unbound volume of distribution. Due to the complicated pharmacokinetic properties of prednisolone, it is extremely difficult to determine the dose needed to obtain a desired target concentration. The pharmacokinetics of methylprednisolone are more predictable because methylprednisolone concentrations are proportional to dose, and no determination of plasma protein binding is needed . J Clin Pharmacol 1997;37:916–925.

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