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Pharmacokinetics of Methylprednisolone Hemisuccinate and Methylprednisolone in Chronic Liver Disease
Author(s) -
Ludwig Elizabeth A.,
Kong AhNg,
Camara Daniel S.,
Jusko William J.
Publication year - 1993
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1993.tb01955.x
Subject(s) - pharmacokinetics , methylprednisolone , urine , volume of distribution , medicine , chemistry , cirrhosis , corticosteroid , endocrinology , pharmacology
The disposition of methylprednisolone (MP) and its prodrug hemisuccinate (MPHS) was assessed in six middle‐aged patients with chronic liver disease (CLD) and compared with six younger, healthy subjects after a single IV dose of 25.4 mg of MPHS. Blood and urine samples were collected over 12 hours. Plasma and urine concentrations of MPHS and MP and plasma cortisol were measured by HPLC. MPHS clearance (CL) was significantly reduced in the CLD group (495 vs. 1389 mL/hr/kg) whereas volume of distribution (V ss ) of MPHS (about 0.35 1/kg) did not differ. The elimination half‐life, t1/2β, was significantly longer in CLD (0.61 vs. 0.32 hr). The percent recovery of unchanged MPHS in urine was similar (about 9%) in both groups. The kinetic parameters of MP did not differ between the two groups for: clearance (about 370 L/hr/kg IBW), Vss (about 1.3 L/kg), and t 1/2β (about 3.0 hr). The suppression t 1/2 of cortisol after MPHS was longer (3.9 vs. 1.9 hr) indicating metabolic pathways for cortisol and MP are affected differently in CLD. Reduction in MPHS CL may reflect altered hepatic blood flow due to both cirrhosis and age effects. However, good availability of MP from MPHS and lack of perturbation of MP pharmacokinetics in CLD patients may provide therapeutic advantages in selection of this glucocorticoid. This is the first study that characterizes the disposition of the prodrug MPHS and the formation of MP simultaneously in CLD patients.