A COMPARATIVE POPULATION PHARMACOKINETIC ANALYSIS FOR METHYLPREDNISOLONE FOLLOWING MULTIPLE DOSING OF 2 PRODRUGS IN PATIENTS WITH ACUTE ASTHMA

Aims TO conduct a randomized, parallel group comparison of the populat ion pharmacokinetics of the two methylprednisolone (MP) prodrugs Prome drol (MP suleptanate) and Solu-Medrol (MP succinate) in patients hospi talized with acute asthma. Methods Ninety volunteers were included in the pharmacokinetic analysis. Each volunteer received a dosage regimen of 40 mg (MP equivalents) i.v. 6 hourly for 48 h. The bio-conversion and disposition of a 40 mg (MP equivalent) i.v. dose of either MP sule ptanate or MP succinate to MP was modelled as a fist order input, and a mono-exponential elimination phase. Results Population modelling ind icated that the only difference in MP pharmacokinetics between MP sule ptanate and MP succinate was in the input rate constant (66.0 h(-1) vs 5.5 h(-1) respectively). Based on individual Bayesian estimates, the exposure of patients to MP was marginally lower for MP suleptanate alt hough the parameter estimates were not significantly different for hal f-life (2.7 h vs 3.0 h), steady-state AUC (2007.0 ng ml(-1) h vs 2321. 0 ng ml(-1) h) and steady-state C-max (698.4 ng ml(-1) vs 647.8 ng ml( -1)) for MP suleptanate and MP succinate respectively. Conclusions It was concluded that for the multiple dosage regimen used in patients wi th acute asthma the systemic exposure to MP following dosing with MP s uleptanate is similar to that arising from MP succinate. In addition t he differences in the pharmacokinetics for the prodrugs resulted in on ly a small difference in the relative bioavailability of MP for MP sul eptanate (0.94) compared with MP succinate.