Study on the Influence of Silymarin Pretreatment on Metabolism and Disposition of Metronidazole

Rajnarayana, K.; Reddy, Mada S.; Vidyasagar, J; Krishna, D. R.

doi:10.1055/s-0031-1296944

Cited by 36 publications

(26 citation statements)

References 11 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some discrepancy between our study and previous in vitro studies may be explained by the use of higher concentrations used to inhibit the P450 enzymes in vitro than physiologically attainable concentrations. One human study investigated the metabolism and disposition of metronidazole among 12 healthy volunteers and suggested induction of intestinal CYP3A4 and P-glycoprotein following a 9-day exposure to 140 mg/d silymarin (Rajnarayana et al, 2004). The reason for this contradictory result on CYP3A4 relative to our findings remains unclear because the daily silymarin dose of the study was lower than what was used in the present study.…”

Section: Resultscontrasting

confidence: 69%

The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity

et al. 2014

View full text Add to dashboard Cite

Milk thistle (Silybum marianum) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders. The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts. In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 (P450) enzymes. However, determining the potential for clinically significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results. The aim of the present study was to determine the effect of a standardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period. CYP1A2, CYP2C9, CYP2D6, and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs, caffeine, tolbutamide, dextromethorphan, and midazolam, to nine healthy volunteers before and after exposure to a standardized milk thistle extract given thrice daily for 14 days. The three most abundant falvonolignans found in plasma, following exposure to milk thistle extracts, were silybin A, silybin B, and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators. The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration. Exposure to milk thistle extract produced no significant influence on CYP1A2, CYP2C9, CYP2D6, or CYP3A4/5 activities.

show abstract

Section: Resultscontrasting

confidence: 69%

The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Silymarin increased the clearance of metronidazole and hydroxymetronidazole by 29.51% and 31.90%, respectively, with a concomitant decrease in half-life, C max and AUC . The effect of silymarin might induce both intestinal P-gp and CYP3A4 upon multiple dose administration (Rajnarayana et al, 2004).…”

Section: Metronidazolementioning

confidence: 99%

Drug–drug interactions of silymarin on the perspective of pharmacokinetics

Lin

Tsai

2009

Journal of Ethnopharmacology

165

116

View full text Add to dashboard Cite

“…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

Study on the Influence of Silymarin Pretreatment on Metabolism and Disposition of Metronidazole

Cited by 36 publications

References 11 publications

The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity

The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity

Drug–drug interactions of silymarin on the perspective of pharmacokinetics

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

Contact Info

Product

Resources

About