Repeated assessment of methylprednisolone pharmacokinetics during chronic immunosuppression in renal transplant recipients.
OBJECTIVE
To compare the pharmacokinetics of methylprednisolone in renal transplant recipients on 2 occasions separated by at least 1 month during chronic immunosuppression.


METHODS
A prospective unblinded trial.


METHODS
Ten renal transplant recipients (aged 25-62 years) evaluated in a public university-affiliated hospital clinic.


METHODS
All patients received their chronic oral dose of methylprednisolone as a 10-20-minute intravenous infusion during the 2 study periods.


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


RESULTS
During study 1, which ranged from 1.2 to 24 months posttransplant, the mean +/- SD methylprednisolone dose was 13.2 +/- 6.4 mg. In study 2 (2.5-38.5 mo posttransplant), the mean dose was 10.6 +/- 3 mg. During both study periods, methylprednisolone concentrations exhibited a monoexponential decline. Considerable variability in methylprednisolone clearance was observed between periods in certain patients. Four of the 10 patients demonstrated a reduction in clearance from study 1 to study 2, which ranged from a 28% to a 53% decrease. Two patients exhibited an increase in clearance of 40% and 49%. The mean +/- SD total body clearance in study 1 was 363 +/- 330 mL/min/kg, whereas the mean volume of distribution was 1.18 +/- 0.53 L/kg. The mean elimination rate constant was 0.29 +/- 0.14 h-1, with a mean serum half-life of 2.87 +/- 1.15 h during the first phase. In study 2, the mean methylprednisolone clearance was 261 +/- 150 mL/min/kg (p > 0.05) and the mean volume of distribution was 0.89 +/- 0.31 L/kg (p > 0.05). The mean serum half-life of methylprednisolone was 2.91 +/- 0.60 h (p > 0.05), with the mean elimination rate constant of 0.25 +/- 0.06 h-1 (p > 0.05).


CONCLUSIONS
These data demonstrate that intrapatient variability in methylprednisolone clearance exists among certain renal allograft recipients. As a result of the observed variability, patients who are continued on the same dose of methylprednisolone during the posttransplant period of chronic immunosuppression will be subjected to a changing pattern of exogenous glucocorticoid exposure. The impact of these changing patterns requires further prospective evaluation.
Tornatore
K M
KM
Department of Pharmacy Practice, School of Pharmacy, State University of New York at Buffalo, USA.
Reed
K A
KA
Venuto
R C
RC
D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D009518:New York; D011446:Prospective Studies; D013997:Time Factors
D008775:Methylprednisolone