Comparative methylprednisolone pharmacokinetics in renal transplant patients receiving double- or triple-drug immunosuppression.
OBJECTIVE
To assess the pharmacokinetics of chronic methylprednisolone therapy in renal transplant patients receiving double-drug (methylprednisolone and azathioprine) and triple-drug (methylprednisolone, azathioprine, and cyclosporine) immunosuppression.


METHODS
Parallel, randomized trial.


METHODS
Fourteen renal transplant recipients (aged 29-65 y) evaluated in a public, university-affiliated hospital clinic.


METHODS
All patients received their chronic oral dose of methylprednisolone via a 10-20-minute intravenous infusion.


METHODS
Serum methylprednisolone concentrations were determined by HPLC and were used to generate pharmacokinetic parameters for this drug.


RESULTS
The mean daily methylprednisolone dosage was 19 +/- 19 mg in the double-drug group and 9 +/- 2 mg in the triple-drug group. Mean serum creatinine concentrations were 124 +/- 44 and 124 +/- 27 mumol/L, respectively. Mean methylprednisolone clearances were similar in both groups: 405 +/- 205 (double-drug) and 373 +/- 365 mL/h/kg (triple-drug) (p > 0.05). Mean steady-state volume of distribution was 1.5 +/- 0.8 L/kg in the double-drug group and 1.3 +/- 0.8 L/kg in the triple-drug group (p > 0.05). Plasma half-life ranged from 1.7 to 4.3 h (mean 2.7) in the double-drug group versus 1.4 to 3.4 h (mean 2.6) in the triple-drug group (p > 0.05).


CONCLUSIONS
These data indicate that cyclosporine had no definitive influence on methylprednisolone disposition. The results reveal a wide variation in methylprednisolone metabolism in renal transplant recipients receiving either a double- or triple-drug immunosuppressive regimen. Typically, methylprednisolone is prescribed according to a standardized dosing protocol that assumes minimal interpatient variation. Therefore, the pharmacokinetic variability noted in this study may have important clinical implications regarding the development of chronic toxicity (e.g., osteoporosis, hypothalamic-pituitary-adrenal suppression) and the attainment of successful immunosuppression.
Tornatore
K M
KM
Center For Clinical Pharmacy Research, State University of New York, Buffalo 14260.
Walshe
J J
JJ
Reed
K A
KA
Holdsworth
M T
MT
Venuto
R C
RC
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D008775:Methylprednisolone