Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits

Abstract

Danggui is a popular traditional Chinese medicinal (TCM) herb which is easily obtained by the public. The effects of Danggui on the pharmacokinetics and pharmacodynamics of warfarin were studied in rabbits. Single subcutaneous doses (2 mg/kg) of warfarin were administered to 6 rabbits with or without 3 days treatment with oral Danggui extracts (2 g/kg twice daily). Plasma warfarin concentrations were measured by high performance liquid chromatography (HPLC) for 72 h after each of the two warfarin doses. The prothrombin time (PT) was measured daily for 3 days both during the Danggui treatment period and after warfarin doses. Danggui treatment did not affect PT on its own, but significantly lowered PT values 3 days after co-treatment with single dose warfarin. No significant variations in the single dose pharmacokinetic parameters of warfarin were observed after Danggui treatment. A separate group of 6 rabbits were given daily subcutaneous doses of warfarin (0.6 mg/kg) to achieve steady state level, followed by 3 day treatment with oral Danggui extract (2 g/kg twice daily). The slight increase in PT was not significant and two rabbits died after day 7 of the treatment period. However, there was no significant difference in steady state concentrations of warfarin after the Danggui treatment. Results indicate that precautionary advice should be given to patients who self-medicate with Danggui or other TCM products while on chronic treatment with warfarin.

Some aspects of toxic contaminants in herbal medicines

“…We reported the clinical observations on interactions between some popular CM herbs and warfarin with experimental animal studies. Danshen (Salvia miltiorrhiza) had effects on both the pharmacodynamics and pharmacokineties of warfarin in rats (Lo et al, 1992), whereas danggui (Angelica sinensis) affected the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits (Lo et al, 1995).…”

Menopause: a review of botanical dietary supplements

“…One case report of male gynecomastia was purportedly caused by dong quai ingestion. 26 No significant adverse effects are reported in the literature; however, a case report 27 and results of animal research 28 suggest a possible herb-drug interaction between donq quai and warfarin. There are numerous dong quai products in the American marketplace, the majority of which are combination preparations.…”

Interaction between warfarin and Chinese herbal medicines

“…A randomised, open-label, controlled study of newly diagnosed ischaemic stroke patients (n = 35) found that two weeks of concomitant use of Panax ginseng extract 1.5 g with warfarin did not significantly affect peak values, INR and PT area under the curve, thus concluding that Panax ginseng did not influence the pharmacological action of warfarin. (27) (9,10) In vitro study (34,36) Animal study (35) Clinical study (11) -CYP1A1, 2C6, 2C11 inhibitor (35) -Displaces warfarin from HSA-warfarin (36) -Antiplatelet effect (34) -Coumarin-containing (33) Clinical study (37) Animal study (38) -CYP3A4 inducer (37) -CYP1A, 2C, 3A inducer (38) Ginkgo Ginkgo biloba Leaf: 银杏; Fruit: 白果 Case report (12,13) In vitro study (41,42) Clinical study (39) -Antiplatelet effect (39) -CYP1A2, 2C9, 2C19, 2E1, 3A4 inhibitor (41,42) Animal study (43) -CYP1A1, CYP1A2, CYP2B, CYP2C, CYP3A inducer (43) Clinical study (14,15,40) In vitro study (44) Dong quai Angelica sinensis Root: 当归 Case report (16) Animal study (45) -Coumarin-containing (33) ---…”

“…(33) Animal steady state studies have found that Dong quai significantly increased PT (45) without any effect on warfarin concentration, suggesting the presence of pharmacodynamics, but not pharmacokinetic interactions.…”