title: A comparative population pharmacokinetic analysis for methylprednisolone following multiple dosing of two prodrugs in patients with acute asthma.
abstract: OBJECTIVE
  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.
  
  
  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 suleptanate or MP succinate to MP was modelled as a first order input, and a mono-exponential elimination phase.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacia & Upjohn Inc, Fleming Way, Crawley, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Parker
authors.forename: P T
authors.initials: PT
authors.lastname: Daley-Yates
authors.forename: S A
authors.initials: SA
authors.lastname: Wood
mesh_terms: D019540:Area Under Curve; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D001499:Bayes Theorem; D001835:Body Weight / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors; D012907:Smoking
chemical_list: D005938:Glucocorticoids; D011355:Prodrugs; D008776:Methylprednisolone Hemisuccinate; C052305:methylprednisolone suleptanate; D008775:Methylprednisolone