Lack of Pharmacokinetic Interaction Between St. John's Wort and Prednisone

Abstract

St. John's wort (SJW) is a popular dietary supplement involved in numerous dietary supplement-drug interactions with prescription and non-prescription drugs. The supplement has been shown to affect the metabolism of various CYP3A4 substrates. The CYP3A4 pathway mediates the metabolism of a large number of drug entities, including the corticosteroids prednisone and prednisolone. To examine the effects of long-term SJW administration on the pharmacokinetics of prednisone and its reversible metabolite prednisolone in male subjects. Eight male subjects participated in this single-dose study. The pharmacokinetics of prednisone and prednisolone were evaluated before and after 28 days of SJW administration. Plasma corticosteroid concentrations were determined using a normal phase high-performance liquid chromatography assay. Model-independent methods were used to evaluate corticosteroid pharmacokinetics. Twenty-eight days of SJW treatment resulted in no significant alterations in the pharmacokinetic parameters for prednisone or prednisolone. Oral administration of prednisone resulted in prednisone mean +/- SD area under the curves (AUCs) of 115.89 +/- 39.52 microg x h/L prior to SJW treatment and 128.76 +/- 32.71 microg x h/L after 28 days of treatment. Prednisolone mean AUCs were 714.19 +/- 153.29 microg x h/L before SJW administration and 700.74 +/- 89.68 microg x h/L after treatment. Concurrent administration of SJW had no significant effect on the single-dose pharmacokinetics of prednisone or metabolic prednisolone in male subjects.