Systemic bioavailability and pharmacokinetics of methylprednisolone in patients with rheumatoid arthritis following 'high-dose' pulse administration.

The absolute and relative bioavailability of two methylprednisolone formulations (capsules and suspension) was determined along with its pharmacokinetics in four arthritic female patients, following an unconventional high-dose pulse of 1 g. Plasma concentrations of the drug were measured by a sensitive and specific high-performance liquid chromatographic (HPLC) procedure. The disposition of methylprednisolone from plasma following intravenous (i.v.) infusion of its succinate ester appeared monoexponential with a mean half-life of 2.4 h and an apparent volume of distribution (Vd) of 50 l (0.87 l/kg). The total body clearance (Cl) averaged 15.12 l/h. Absolute bioavailability was assessed by comparing the areas under the plasma concentration time curves (normalized to dose) following oral administration of capsule or suspension with those of intravenous administration. No significant difference (p greater than 0.2) was observed when systemic availability (f, expressed in per cent) following administration of drug in capsule (f = 49.35 per cent) was compared with that obtained following the administration of drug in a suspension (f = 58.26 per cent). The difference in the observed and predicted f may be due to incomplete absorption, hepatic and/or extrahepatic metabolism of methylprednisolone. Subjective evaluation showed no side effects of this high-dose pulse therapy in any of the patients.