Figure

Clinical trials of St. John�s wort-drug interactions

[Posted as supplied by authors (but with reference numbers to match main article�s reference list)]

Clinical trials of St. John�s wort-drug interactions

Name and Year	Drug	Participants	Duration of dosing with SJW	Primary Outcomes measured	Interaction
Mathijssen RHJ 2002⁵	Irenotecan	5 cancer patients (2 colorectal, 2 lung, 1 sarcoma) (3 women and 2 men) Median age 58 (Age range 54-66)	18 days	Plasma levels of SN 38 and APC (AUC 0-25)	� AUC by 42% (95% CI, -14 to 70)
Markowitz JS (1) 2000¹⁶	Dextromethorphan (DM) and alprazolam	7 healthy volunteers (3 women and 4 men) (Age range 24-32)	3 days	Plasma levels of Dextromethorphan and alprazolam (AUC 0.5-60)	� AUC by 41% (95% CI, -102 to 19)
Burstein AH 2000¹⁴	Carbamazepine	8 healthy volunteers (Age range 24-43)	14 days	Carbamazepine and carmazapine 10,11 epoxide (AUC 0-24)	NS. 0.01% change (95% CI, -13 to 15)
D�rr D 2000²⁰	Digoxin	8 healthy male volunteers Mean age 27 (23-35)	14 days	Plasma level of Digoxin (AUC 0-7) Expression of intestinal P-glycoprotein / MDR1 CYP3A4 and hepatic CYP3A4 function	Induction of functional expression of intestinal P-glycoprotein / MDRI CYP3A4 and their hepatic CYP3A4
Piscitelli S 2000²¹	Indinavir	8 healthy volunteers, 6 men (Age range 29-50)	14 days	Indinavir (AUC 0-8)	� AUC by 54% (95% CI, -67 to �42)
Mai I 2003⁷	Tacrolimus and Mycophenic acid	10 renal transplant patients (6 men and four women). 8 received mycophenic acid.	14 days	Tacrolimus and mycophenolic acid plasma levels (AUC 0-12)	Tacrolimus levels � by 52% (95% CI, -61 to �44) Mycophenolic acid NS � 4.5%
Hebert M 2004²³	Tacrolimus	10 healthy volunteers (8 women and 2 men) (Age range 20-30)	18 days	Tacrolimus (AUC 0-14)	� AUC by 35% (95% CI, -56 to -14)
Bauer S 2003⁶	Cyclosporin A	11 renal transplant patients. 9 men, 2 women (Age range: 34-59)	14 days	Plasma concentrations of Cyclosporin and related metabolites (AUC 0-12)	AUC: 45% � (95% CI, -55 to -36)
Hall S 2004⁸	Oral contraceptive and midazolam	12 healthy premenopausal women using oral contarception (>3 months) (Mean age 27 SD 7)	2 cycles	Serum concentrations of ethinyl estradiol, norethindrone, FSH, luteinizing hormone, progesterone and midazolam (AUC 0-24)	Systemic clearance of midazolam was unchanged (� -6%, 95%CI-10 to 2).
Jiang X 2004²²	Warfarin	12 healthy men (Age range 20-40)	14 days	Warfarin (AUC -48-� ₎	� AUC of S-warfarin by 27.7% (95% CI, -16 to -38)
Johne A (2) 2001⁴	Amitriptyline	12 patients requiring tricyclic antidepressants (9 women and 3 men) Mean age 47 (24-72)	14-16 days	Amitriptyline (AUC 0-12)	� AUC by 22% (95% CI, -27 to �17)
Wang Z (1) 2001¹⁰	Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6), oral midazolam (intestinal wall and hepatic CYP3A), and intravenous midazolam (hepatic CYP3A)	12 healthy volunteers (5 women, 7 men) (Mean age 29 � 6)	Single dose and 14 days	Plasma levels of probe drugs AUC (0-72)	Long-term administration resulted in 52% decrease of midazolam (95% CI, 0 to 104). It did not alter the CYP2C9, CYP1A2, or CYP2D6 activities.
Wang Z (2) 2002⁹	Fexofenadine	12 healthy volunteers (9 women and 3 men) (Mean age 32 � 7)	Single dose and 14 days	Plasma levels of fexofenadine and oral clearance. AUC (0-48)	Long term: � AUC by 10% (95% CI ,-44 to 25) Oral clearance � of 47%
Markowitz JS (2) 2003²⁴	Dextromethorphan and alprazolam	12 healthy volunteers (6 women and 6 men. Mean age 28.6 years, range 22-38)	14 days	Plasma levels of alprazolam and urine levels of DM metabolite (AUC 0.5-60)	� AUC of alprazolam by 53% (95% CI, -70 to -37)
Dresser GK 2003²⁵	Midazolam, Fexofenadine, Cyclosporine	21 healthy volunteers (10 men: mean age:24.4� 3.8; 11 women: mean age 35.3� 10.4)	12 days	Plasma concentration of midazolam , cyclosporine and fexofenadine, (AUC 0-24)	Midazolam: Systemic clearance � 52% (95% CI, -68 to �36)
Roby C 2001¹¹	Dextromethorphan	13 healthy volunteers (9 women and 4 men) 30� 7.5	14 days	DM metabolites in urine	NS: 0.5% change (95% CI, -90 to 100)
Wenk M 2004¹²	Caffeine, DM	16 healthy volunteers (8 women and 8 men) (25-58 years)	14 days	Caffeine DM metabolites in urine	CYP 3A4 activity � 82% (95% CI, 20-137)
Sugimoto K (1,2) 2001¹⁵	Simvastatin or pravastatin	8 healthy men Mean age 32.8 (26-44) in group I (1) 8 healthy men Mean age 33.3(27-46) in group II (2)	14 days	Simvastatin and pravastatin (AUC 0-24)	Simvastatin: � AUC by 53% (95% CI, -131 to 24) Pravastatin: NS: � of 12% (95%CI, -53 to 30)
Pfrunder A 2003¹⁷	Oral contraceptive	17 healthy women (Age range 20-35)	2 cycles	Diametre of follicle-like structure (FLS) within ovaries, breakthrough bleeding and AUC 0-24 of ethinyloestradiol and 3-ketodesogestrel	AUC of 3-ketodesogestrel � 43.9% (95% CI, -49 to �39)
Wang L 2004¹⁸	Omeprazole	12 healthy men Age range 18-25	14 days	Omeprazole plasma concentration with metabolites (AUV 0-12)	� 49% (95% CI, -64 to �34)
Morimoto T 2004¹⁹	Theophylline	12 healthy men Mean age 25 SD 6.4	15 days	Plasma Theophylline (AUC 0-48)	� AUC by 3% (95% CI, -6 to �1)
Johne A (1) 1999¹³	Digoxin	25 healthy volunteers (12 women and 13 men) mean age 26 (22-33)	10 days	Digoxin concentration profiles at days 5,6, and 15 (AUC 0-24)	� AUC by 25% (95% CI, -31 to -19)

Legend: AUC, Area Under the Concentration time Curve; C_max, Concentration maximum; � , increase; � , decrease; qid, four times per day/ tid, three times per day/ bid, two times per day;