Pharmacokinetics of Methylprednisolone in Elderly and Young Healthy Males

OBJECTIVE: To characterize and compare the pharmacokinetics of a single intravenous dose of methylprednisolone in elderly and young healthy males. DESIGN : A randomized, parallel pharmacokinetic trial. SETTING : A public university‐affiliated hospital. SUBJECTS : Seven healthy, elderly white males (aged 69 to 82 years) and five healthy, young white males (aged 24 to 37 years) who gave informed consent and fulfilled all screening criteria. MEASUREMENTS : Serial blood samples were obtained over a 24‐hour study period after intravenous administration of a 10‐mg dose of methylprednisolone. Serum methylprednisolone concentrations were determined by high performance liquid chromatography and utilized to determine the pharmacokinetic parameters. RESULTS : Methylprednisolone serum concentrations declined in a linear manner in both groups. However, 4 hours after the dose, the mean serum concentration of methylprednisolone was 50.9 ± 15.1 ng/mL in the elderly group and 37.6 ± 7.5 ( P = 0.07) ng/mL in the young group. The clearance of methylprednisolone was 237 ± 62 mL/h/kg, with a volume of distribution of 1.10 ± 0.07 L/kg, for the elderly group, whereas the young males had a mean drug clearance of 359 ± 90 mL/h/kg ( P < 0.05) and a mean volume of distribution of 1.28 ± 0.34 L/kg. The half‐life of methylprednisolone ranged from 1.90 to 5.40 hours in the elderly group; the range was 1.99 to 3.31 hour ( P = 0.16) in the young group. CONCLUSION : A slower methylprednisolone clearance was noted in the elderly group compared with the young counterparts. This pharmacokinetic alteration seen in healthy elderly subjects may contribute to the increased incidence of adverse effects from chronic glucocorticoid therapy that has been observed among elderly patients.