Lack of pharmacokinetic interaction between St. John's wort and prednisone.
BACKGROUND
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.


OBJECTIVE
To examine the effects of long-term SJW administration on the pharmacokinetics of prednisone and its reversible metabolite prednisolone in male subjects.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Concurrent administration of SJW had no significant effect on the single-dose pharmacokinetics of prednisone or metabolic prednisolone in male subjects.
Bell
Edward C
EC
College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA. bellec@tsu.edu
Ravis
William R
WR
Chan
Hui Min
HM
Lin
Yuh-Jing
YJ
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000097:blood / Q000493:pharmacokinetics*; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D008297:Male; D028321:Plant Preparations / Q000494:pharmacology*; D010946:Plants, Medicinal; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics*; D011241:Prednisone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D005938:Glucocorticoids; D028321:Plant Preparations; D003577:Cytochrome P-450 Enzyme System; D011239:Prednisolone; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D011241:Prednisone