Interaction of St John's wort with conventional drugs: systematic review of clinical trials
BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.329.7456.27 (Published 01 July 2004) Cite this as: BMJ 2004;329:27
Data supplement
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)
Dürr 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 λ 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 λ 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 λ 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 λ 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; Cmax, Concentration maximum; λ , increase; ¯ , decrease; qid, four times per day/ tid, three times per day/ bid, two times per day;
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