methylprednisolone-suleptanate and Body-Weight

To conduct a randomized, parallel group comparison of the population pharmacokinetics of the two methylprednisolone (MP) prodrugs Promedrol (MP suleptanate) and Solu-Medrol (MP succinate) in patients hospitalized with acute asthma.. 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 suleptanate or MP succinate to MP was modelled as a first order input, and a mono-exponential elimination phase.. Population modelling indicated that the only difference in MP pharmacokinetics between MP suleptanate 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 although the parameter estimates were not significantly different for half-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 Cmax (698.4 ng ml-1 vs 647.8 ng ml-1) for MP suleptanate and MP succinate respectively.. It was concluded that for the multiple dosage regimen used in patients with acute asthma the systemic exposure to MP following dosing with MP suleptanate is similar to that arising from MP succinate. In addition the differences in the pharmacokinetics for the prodrugs resulted in only a small difference in the relative bioavailability of MP for MP suleptanate (0.94) compared with MP succinate.

Topics: Area Under Curve; Asthma; Bayes Theorem; Body Weight; Chromatography, High Pressure Liquid; Double-Blind Method; Female; Glucocorticoids; Half-Life; Humans; Injections, Intravenous; Male; Methylprednisolone; Methylprednisolone Hemisuccinate; Prodrugs; Sex Factors; Smoking

To establish the regimen for beneficial prolonged treatment with glucocorticoids on nephritis, we investigated the antinephritic effect of methylprednisolone suleptanate (MPS) and its influence on adrenal function by intermittent administration (IA) in comparison with daily administration (DA) in crescentic-type anti-GBM nephritic rats. In IA, MPS (0.25, 1.0 and 3.0 mg/kg) was injected for 3 successive days followed by a 3-day withdrawal during a 40-day period. MPS inhibited the elevation of urinary protein and serum cholesterol and glomerular alterations by both IA and DA. The effect of MPS on these parameters was more potent by IA than by DA. MPS significantly suppressed the increment of the number of ED-1(+) cells and TH-1(+) cells in nephritic glomeruli. DA, but not IA, caused atrophy of the adrenal glands. IA prevented the remarkable decrease in corticosterone level provoked in nephritic rats. In conclusion, for the treatment of nephritis, IA seems to be a better regimen for the administration of MPS. MPS may exert an antinephritic action by inhibiting mesangial cell proliferation and infiltration of monocytes/macrophages into glomeruli in addition inhibiting antibody production.

Topics: Adrenal Glands; Animals; Antibodies; Basement Membrane; Body Weight; Cholesterol; Corticosterone; Creatinine; Drug Administration Schedule; Glomerular Mesangium; Glomerulonephritis; Kidney Glomerulus; Macrophages; Male; Methylprednisolone; Monocytes; Organ Size; Proteinuria; Rats; Rats, Sprague-Dawley