Effect of Milk Thistle on the Pharmacokinetics of Indinavir in Healthy Volunteers

Piscitelli, Stephen C.; Formentini, Elizabeth; Burstein, Aaron H.; Alfaro, Raul M.; Jagannatha, Shyla; Falloon, Judith

doi:10.1592/phco.22.8.551.33205

Cited by 126 publications

(83 citation statements)

References 7 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Serial blood and urine concentrations demonstrate that milk thistle did not inhibit these CYPs. Two subsequent studies conducted in healthy volunteers showed that milk thistle did not alter the pharmacokinetics of midazolam, 35 irinotecan, 172 idinavir, [173][174][175] and nifedipine, 176 known substrates of CYP3A4, confirming the results of the earlier study. Furthermore, milk thistle does not affect UGT1A activity because the pharmacokinetics of irinotecan was not altered after milk thistle supplementation 172 ; irinotecan undergoes extensive catabolism by this UGT.…”

Section: Human and Clinical Studiessupporting

confidence: 78%

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

2009

View full text Add to dashboard Cite

Many Americans use complementary and alternative medicine (CAM) to prevent or alleviate common illnesses, and these medicines are commonly used by individuals with cancer. These medicines or botanicals share the same metabolic and transport proteins, including cytochrome P450 enzymes (CYP), glucuronosyltransferases (UGTs), and P-glycoprotein (Pgp), with over-thecounter and prescription medicines increasing the likelihood of drug-botanical interactions. This review provides a brief description of the different proteins, such as CYPs, UGTs, and Pgp. The potential effects of drug-botanical interactions on the pharmacokinetics and pharmacodynamics of the drug or botanical and a summary of the more common models used to study drug metabolism are described. The remaining portion of this review summarizes the data extracted from several laboratory, animal, and clinical studies that describe the metabolism, transport, and potential interactions of 8 selected botanicals. The 8 botanicals include black cohosh, Echinacea, garlic, Gingko biloba, green tea, kava, milk thistle, and St John's wort; these botanicals are among some of the more common botanicals taken by individuals with cancer. These examples are included to demonstrate how to interpret the different studies and how to use these data to predict the likelihood of a clinically significant drug-botanical interaction.

show abstract

Section: Human and Clinical Studiessupporting

confidence: 78%

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

2009

View full text Add to dashboard Cite

show abstract

“…The interaction between milk thistle and antiretroviral drugs was studied several years ago in healthy volunteers who received indinavir with or without multiple doses of silymarin (8,30,36). Administration of silymarin also failed to influence the indinavir AUC in these studies, although slight reductions in indinavir trough concentrations were observed.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical studies with milk thistle have produced discordant results regarding its ability to modulate these proteins in vivo (7,12,14,15,17,37), and evidence on the interaction between milk thistle and antiretroviral drugs comes from clinical trials that have not used currently recommended treatment regimens (8,30,36).…”

mentioning

confidence: 99%

Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients

Moltó

Valle

Miranda

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement milk thistle (silymarin) to interact with the boosted protease inhibitor combination darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy with darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included. Silymarin (150 mg every 8 h) was added to the antiretroviral treatment from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavirritonavir on day 0 and darunavir-ritonavir plus silymarin on day 14. Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 by means of the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 48 years (interquartile range, 44 to 50 years), and the median body weight was 70 kg (interquartile range, 65 to 84 kg). Silymarin was well tolerated, and all participants completed the study. The GMRs for darunavir coadministered with silymarin relative to darunavir alone were 0.86 (90% CI, 0.70 to 1.05) for the area under the concentration-time curve from 0 to 12 h, 0.83 (90% CI, 0.80 to 0.98) for the maximum concentration, and 0.94 (90% CI, 0.73 to 1.19) for the concentration at the end of the dosing interval. In summary, coadministration of silymarin with darunavirritonavir seems to be safe in HIV-infected patients; no dose adjustment for darunavir-ritonavir seems to be necessary.

show abstract

“…Milk thistle also did not influence the PK of the protease inhibitor indinavir in two independent studies [82,83]. However, a recent study [84] showed that 8 days of echinacea treatment in volunteers resulted in a 34% greater systemic clearance of midazolam and a significantly lower AUC.…”

Section: Pk Studies In Humansmentioning

confidence: 94%

Herb–Drug Interactions in Oncology: Focus on Mechanisms of Induction

2006

View full text Add to dashboard Cite

An increasing number of cancer patients are using complementary and alternative medicines (CAM) in combination with their conventional chemotherapeutic treatment. Considering the narrow therapeutic window of oncolytic drugs, this CAM use increases the risk of clinically relevant herb-anticancer drug interactions. Such a relevant interaction is that of St. John's wort with the anticancer drugs irinotecan and imatinib. It is, however, estimated that CAM-anticancer drug interactions are responsible for substantially more unexpected toxicities of chemotherapeutic drugs and possible undertreatment seen in cancer patients.Induction of drug-metabolizing enzymes and ATP-binding cassette drug transporters can be one of the mechanisms behind CAM-anticancer drug interactions. Induction will often lead to therapeutic failure because of lower plasma levels of the anticancer drugs, and will easily go unrecognized in cancer treatment, where therapeutic failure is common.Recently identified nuclear receptors, such as the pregnane X receptor, the constitutive androstane receptor, and the vitamin D-binding receptor, play an important role in the induction of metabolizing enzymes and drug transporters. This knowledge has already been an aid in the identification of some CAM probably capable of causing interactions with anticancer drugs: kavakava, vitamin E, quercetin, ginseng, garlic, β-carotene, and echinacea. Evidently, more research is necessary to prevent therapeutic failure and toxicity in cancer patients and to establish guidelines for CAM use. The Oncologist 2006;11:742-752 Learning ObjectivesAfter completing this course, the reader will be able to:1. Describe the possible pharmacokinetic interactions between complementary alternative medicines and oncolytic drugs and the clinical consequences thereof.2. Define the role of the nuclear receptors PXR, CAR, and VDR in herb-drug interactions.3. Discuss methods to measure induction of drug-metabolizing enzymes and transporters.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit

show abstract

Effect of Milk Thistle on the Pharmacokinetics of Indinavir in Healthy Volunteers

Abstract: Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.

Cited by 126 publications

References 7 publications

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

Drug—Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals

Effect of Milk Thistle on the Pharmacokinetics of Darunavir-Ritonavir in HIV-Infected Patients

Herb–Drug Interactions in Oncology: Focus on Mechanisms of Induction

Contact Info

Product

Resources

About