MILK THISTLE (SILYBUM MARIANUM)The

MILK THISTLE (SILYBUM MARIANUM)

The popularity of milk thistle is due to the purported hepatoprotectant properties of silymarin, a mixture of flavanolignans (e.g., silibinin A, silibinin B, silichristin, silidianin, taxifolin) extracted from the seeds of Silybum marianum. Indicated for the treatment and prevention of various liver diseases, silymarin has a good safety profile, but its mechanism of action is unclear.109 Another uncertainty is the drug interaction potential of silymarin. Two groups using in vitro models have recently

documented inhibitory effects of either milk thistle extract or silibinin on human drug metabolizing enzymes.110,111 Of the enzymes investigated, only CYP3A4, CYP2C9, and uridine diphosphoglucuronsyl transferase were inhibited at concen- trations similar to those observed in vivo. Reports detailing the pharmacokinetics of silibinin in humans have yielded varied results.109,112 Oral administration of silymarin extract in doses from 120 to 360 mg produced serum concentrations of silibinin and its glucuronide and sulfate conjugates in the range of 100 to 1400 ng/mL, while bile concentrations reached 100 times those of serum, indicating extensive biliary secre- tion.109 Thus, when administered orally, concentrations of silymarin components may be sufficiently high to compete for CYP binding sites in the liver and gut wall. In vivo evidence for CYP-mediated milk thistle interactions, however, is less compelling. Administration of silymarin (Legalon, 70 mg, three times daily) for 28 days to healthy volunteers had no effect on the pharmacokinetics of aminopyrine or phenylbutazone.113 Following 21 days of milk thistle extract administration (153 mg silymarin, three times daily) no clinically significant changes in the pharmacokinetics of indinavir (partial CYP3A4 substrate) were noted in human subjects.114 Similarly, 28 days of milk thistle extract supplementation to human volunteers (110 mg sily- marin, twice daily) reduced midazolam clearance (CYP3A4 substrate) an average of only 13%.115 This seeming lack of in vitro/in vivo correlation may stem from poor bioavailability, large interindividual variations in silibinin absorption, lower CYP binding affinities of silibinin conjugates, poor dissolution characteristics of milk
thistle dosage forms, or interproduct variability in silymarin content.109,116 Interestingly, enhanced activity of phase II enzymes (e.g., glutathione S-trans-
ferase, quinone reductase) has been noted in mice following prolonged administra- tion of large silibinin doses.117 Whether similar effects occur in humans, however, remains to be determined.

Hasil (Bahasa Indonesia) 1:

MILK THISTLE (SILYBUM MARIANUM)Popularitas milk thistle adalah karena sifat diakui hepatoprotectant silymarin, campuran flavanolignans (misalnya, silibinin A, silibinin B, silichristin, silidianin, taxifolin) diekstrak dari biji Silybum marianum. Diindikasikan untuk pengobatan dan pencegahan berbagai penyakit hati, silymarin memiliki profil keamanan yang baik, tapi mekanisme kerjanya unclear.109 ketidakpastian lain adalah interaksi obat potensi silymarin. Dua kelompok yang menggunakan secara in vitro model baru-baru ini documented inhibitory effects of either milk thistle extract or silibinin on human drug metabolizing enzymes.110,111 Of the enzymes investigated, only CYP3A4, CYP2C9, and uridine diphosphoglucuronsyl transferase were inhibited at concen- trations similar to those observed in vivo. Reports detailing the pharmacokinetics of silibinin in humans have yielded varied results.109,112 Oral administration of silymarin extract in doses from 120 to 360 mg produced serum concentrations of silibinin and its glucuronide and sulfate conjugates in the range of 100 to 1400 ng/mL, while bile concentrations reached 100 times those of serum, indicating extensive biliary secre- tion.109 Thus, when administered orally, concentrations of silymarin components may be sufficiently high to compete for CYP binding sites in the liver and gut wall. In vivo evidence for CYP-mediated milk thistle interactions, however, is less compelling. Administration of silymarin (Legalon, 70 mg, three times daily) for 28 days to healthy volunteers had no effect on the pharmacokinetics of aminopyrine or phenylbutazone.113 Following 21 days of milk thistle extract administration (153 mg silymarin, three times daily) no clinically significant changes in the pharmacokinetics of indinavir (partial CYP3A4 substrate) were noted in human subjects.114 Similarly, 28 days of milk thistle extract supplementation to human volunteers (110 mg sily- marin, twice daily) reduced midazolam clearance (CYP3A4 substrate) an average of only 13%.115 This seeming lack of in vitro/in vivo correlation may stem from poor bioavailability, large interindividual variations in silibinin absorption, lower CYP binding affinities of silibinin conjugates, poor dissolution characteristics of milkbentuk sediaan Thistle, atau interproduct variabilitas dalam silymarin content.109,116 Menariknya, peningkatan aktivitas enzim tahap II (misalnya, glutathione S - trans-ferase, quinone reduktase) telah dicatat pada tikus yang mengikuti pemerintahan-tion berkepanjangan dari besar silibinin doses.117 Apakah efek yang sama terjadi pada manusia, namun, masih harus ditentukan.