The Effects of St. John's Wort on the Pharmacokinetics of Corticosteroid and Non-Steroidal Drug Preparations

Abstract

St. John’s Wort is a flowering plant whose extracts have gained increasing popularity in the treatment of mild to moderate depression. This investigation examined the impact of long-term St. John’s Wort administration upon the pharmacokinetic profiles of the glucocorticoid drugs prednisone and prednisolone, and upon the pharmacokinetic profile of enantiomeric ibuprofen. The pharmacokinetics of prednisone and prednisolone were not significantly changed by St. John’s Wort co-administration. Mean prednisone parameters (for control samples and St. John’s Wort treatment samples, respectively) were 3.85 +/- 1.49 hrs and 5.10 +/- 2.77 hrs for drug elimination half-life, 115.89 +/- 39.52 µg*hr/L and 128.76 +/- 32.71µg*hr/L for area under the curve (AUC), 15.42 +/- 4.19 µg/L and 15.11 +/- 3.41 µg/L for maximum plasma concentration (Cmax), and 6.44 +/- 0.92 hrs and 8.56 +/- 3.88 hrs for mean residence time (MRT). Mean prednisolone parameters (for control samples and St. John’s Wort treatment samples, respectively) were 2.97 +/- 0.59 hrs and 3.09 +/- 0.83 hrs for drug elimination half-life, 714.19 +/- 153.29 µg*hr/L and 700.74 +/- 89.68 µg*hr/L for AUC, 128.10 +/- 25.33 µg/L and 128.58 +/- 23.65 µg/L for Cmax, and 5.03 +/- 0.88 hrs and 5.23 +/- 1.23 hrs for MRT. Average ratios of prednisolone to prednisone AUC were 6.40 +/- 0.970 and 5.64 +/- 1.15 before and after St. John’s Wort co-administration, respectively. Minimal significant changes in ibuprofen pharmacokinetics resulted from long-term St. John’s Wort therapy. Mean S(+)-ibuprofen parameters (for control samples and St. John’s Wort treatment samples, respectively) were 3.24 +/- 1.61 hrs and 2.17 +/- 0.477 hrs for drug elimination half-life, 131.6 +/- 26.8 µg*hr/mL and 122.4 +/- 32.9 µg*hr/mL for AUC, 31.8 +/- 7.33 µg/mL and 33.6 +/- 7.83 µg/mL for Cmax, and 5.20 +/- 1.95 hrs and 3.60 +/- 0.322 hrs for MRT. A clinically significant decrease in Senantiomer mean residence time was seen following St. John’s Wort treatment. Mean R(-)-ibuprofen parameters (for control samples and St. John’s Wort treatment samples, respectively) were 2.28 +/- 1.34 hrs and 1.55 +/- 0.641 for drug elimination half-life, 85.1 +/- 26.6 µg*hr/mL and 87.7 +/- 30.1 µg*hr/mL for AUC, and 28.4 +/- 8.72 µg/mL and 30.0 +/- 8.97 µg/mL for Cmax, and 3.76 +/- 1.71 hrs and 2.78 +/- 0.631 hrs for MRT. Average ratios for S- to R-enantiomer AUC were 1.69 +/- 0.654 before St. John’s Wort dosing and 1.49 +/- 0.496 after St. John’s Wort co-administration, respectively.