The Clinical Pharmacology of Methylprednisolone Sodium Phosphate. I. Intramuscular Route of Administration

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Abstract
I.m. administered methylprednisolone sodium phosphate (Medrol Stabisol) in single doses of 40, 80 or 160 mg (methylprednisolone equivalents) had a similar effect as the same doses of methylprednisolone sodium succinate (Solu-Medrol) with regard to eosinophil suppression, elevation of glucose, white blood count differential shifts (lympholytic effect), urinary excretion of Na and K and localized (pain) and systemic side effects. The average plasma methylprednisolone concentration was .apprx. 20% higher after the i.m. administration of methylprednisolone sodium phosphate than after methylprednisolone sodium succinate. The differences in plasma methylprednisolone levels produced by the 2 esters suggest that hydrolysis of the succinate ester occurs more slowly or the succinate ester distributes more extensively. This difference in plasma level is not reflected in any other pharmacologic evaluation of the 2 esters, e.g., both eosinophil depression and hyperglycemic response were identical. No clinically significant changes in vital signs, standard hematology and clinical chemistry parameters evaluated were noted after 21 successive doses (q.i.d. [4 .times. per day] for 5 days with 1 dose in the morning of day 6) of 80 mg methylprednisolone sodium phosphate. An increase was noted in the systolic blood pressure from a pretreatment mean of 113 mm Hg to a posttreatment mean of 123 mm Hg and an increase in the body wt from a pretreatment mean of 177 pounds to a posttreatment mean of 183 pounds. No signs of adrenal suppression were found as judged by plasma cortisol and ACTH levels. Six (6/12) subjects of the methylprednisolone sodium phosphate group, 1 subject of the vehicle group and 1 subject of the placebo (sterile saline) group reported the following systemic side effects: gas in stomach, headaches, anorectal itching and dryness or itching of the skin. No trend was observed for any side effect reported. In these double-blind, randomized studies, single (40, 80 and 160 mg) and multiple (80 mg) i.m. doses of methylprednisolone sodium phosphate were tolerated in healthy volunteers and the same doses of methylprednisolone sodium succinate and similar volumes of vehicle or placebo.