PMC:4100259 / 17348-20137
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/4100259","sourcedb":"PMC","sourceid":"4100259","source_url":"http://www.ncbi.nlm.nih.gov/pmc/4100259","text":"4.3. In Vivo Studies\nIn an in vivo study on mice, a valerian extract (aqueous ethanolic, not further described), given in a dose of 0.5% with the diet over 28 days (corresponding to a daily dose of 595 mg/kg in average) did neither affect the CYP content of the liver nor the activities of CYP 1A1, CYP 1A2, CYP 2C9, and CYP 3A4 [34].\nIn twelve healthy volunteers (6 males and 6 females, age 30.9 ± 7.2 years, nonsmokers from South Carolina), the effect of a valerian root extract on the activity of the drug-metabolizing enzymes CYP 2D6 and CYP 3A4 was tested [37]. Daily before going to bed, participants took two tablets, with 500 mg valerian extract each (extraction solvent ethanol 70%, valerenic acid content 5.51 mg/tablet), for 14 subsequent days. This dose is well within the range of recommended doses for valerian preparations. The probe drugs dextromethorphan (30 mg; CYP 2D6 activity) and alprazolam (2 mg; CYP 3A4 activity) were administered orally at baseline and after treatment with valerian, and dextromethorphan to dextrorphan metabolic ratios and alprazolam pharmacokinetics were determined. The ratio of dextromethorphan to dextrorphan increased slightly but significantly from 0.214 to 0.254. The maximum concentration of alprazolam was moderately increased for about 20% from 25 to 31 ng/mL (P \u003c 0.05). This change is therefore within the frame of 80% to 125% rated as equivalent by FDA. Bioavailability of other medicines would therefore not be relevantly diminished and therapeutic efficacy of a therapy not questioned. Changes of other pharmacokinetic parameters were not detected. In conclusion valerian in therapeutic doses is unlikely to produce clinically relevant effects on CYP 2D6 and CYP 3A4 pathways which could diminish the therapeutic efficacy of other drugs.\nIn another study, twelve healthy volunteers (six men and six women, age mean ± SD = 24 ± 3 years, weight 69.3 ± 14.2 kg KGW) were randomly assigned to receive valerian (DER 4 : 1, no standardization claim) for 28 days, three times daily 125 mg [35]. Before and after the test period, the activities of CYP 3A4/5 (1-hydroxymidazolam/midazolam serum ratio), CYP 1A2 (paraxanthine/caffeine serum ratio), CYP 2E1 (hydroxychlorzoxazone/chlorzoxazone serum ratio), and CYP 2D6 (debrisoquine urinary recovery ratio) were determined. All subjects were nonsmokers and extensive metabolizers of CYP 2D6. No changes at all in phenotypic ratios were observed. The daily dose applied in this study was corresponding to 1.5 g drug, which is in the lower range of doses recommended, for example, in the monograph of the HMPC. Despite that, the fact that there was not even a tendency of an effect in the CYP isoenzymes tested underlines the assumption of the lack of an interaction potential in CYP enzymes.","divisions":[{"label":"Title","span":{"begin":0,"end":20}}],"tracks":[{"project":"NEUROSES","denotations":[{"id":"T294","span":{"begin":2657,"end":2665},"obj":"PATO_0002360"},{"id":"T235","span":{"begin":211,"end":218},"obj":"PATO_0000461"},{"id":"T236","span":{"begin":220,"end":223},"obj":"CHEBI_52027"},{"id":"T237","span":{"begin":243,"end":246},"obj":"CHEBI_38559"},{"id":"T238","span":{"begin":290,"end":293},"obj":"CHEBI_38559"},{"id":"T239","span":{"begin":299,"end":302},"obj":"CHEBI_38559"},{"id":"T240","span":{"begin":308,"end":311},"obj":"CHEBI_38559"},{"id":"T241","span":{"begin":321,"end":324},"obj":"CHEBI_38559"},{"id":"T242","span":{"begin":530,"end":533},"obj":"CHEBI_38559"},{"id":"T243","span":{"begin":542,"end":545},"obj":"CHEBI_38559"},{"id":"T244","span":{"begin":880,"end":883},"obj":"CHEBI_38559"},{"id":"T245","span":{"begin":920,"end":923},"obj":"CHEBI_38559"},{"id":"T246","span":{"begin":1706,"end":1709},"obj":"CHEBI_38559"},{"id":"T247","span":{"begin":1718,"end":1721},"obj":"CHEBI_38559"},{"id":"T248","span":{"begin":2099,"end":2102},"obj":"CHEBI_38559"},{"id":"T249","span":{"begin":2153,"end":2156},"obj":"CHEBI_38559"},{"id":"T250","span":{"begin":2260,"end":2263},"obj":"CHEBI_38559"},{"id":"T251","span":{"begin":2382,"end":2385},"obj":"CHEBI_38559"},{"id":"T252","span":{"begin":2686,"end":2689},"obj":"CHEBI_38559"},{"id":"T253","span":{"begin":2777,"end":2780},"obj":"CHEBI_38559"},{"id":"T254","span":{"begin":247,"end":254},"obj":"PATO_0000025"},{"id":"T255","span":{"begin":707,"end":714},"obj":"PATO_0000025"},{"id":"T256","span":{"begin":388,"end":391},"obj":"PATO_0000011"},{"id":"T257","span":{"begin":1865,"end":1868},"obj":"PATO_0000011"},{"id":"T258","span":{"begin":388,"end":391},"obj":"CHEBI_84123"},{"id":"T259","span":{"begin":1865,"end":1868},"obj":"CHEBI_84123"},{"id":"T260","span":{"begin":504,"end":508},"obj":"CHEBI_23888"},{"id":"T261","span":{"begin":849,"end":854},"obj":"CHEBI_23888"},{"id":"T262","span":{"begin":1790,"end":1795},"obj":"CHEBI_23888"},{"id":"T263","span":{"begin":2509,"end":2513},"obj":"CHEBI_23888"},{"id":"T264","span":{"begin":671,"end":678},"obj":"CHEBI_46787"},{"id":"T265","span":{"begin":679,"end":686},"obj":"CHEBI_44730"},{"id":"T266","span":{"begin":679,"end":686},"obj":"CHEBI_16236"},{"id":"T267","span":{"begin":843,"end":848},"obj":"CHEBI_50406"},{"id":"T268","span":{"begin":855,"end":871},"obj":"CHEBI_4470"},{"id":"T269","span":{"begin":1014,"end":1030},"obj":"CHEBI_4470"},{"id":"T270","span":{"begin":1125,"end":1141},"obj":"CHEBI_4470"},{"id":"T271","span":{"begin":902,"end":912},"obj":"CHEBI_2611"},{"id":"T272","span":{"begin":1067,"end":1077},"obj":"CHEBI_2611"},{"id":"T273","span":{"begin":1244,"end":1254},"obj":"CHEBI_2611"},{"id":"T274","span":{"begin":1034,"end":1045},"obj":"CHEBI_29133"},{"id":"T275","span":{"begin":1145,"end":1156},"obj":"CHEBI_29133"},{"id":"T276","span":{"begin":1116,"end":1121},"obj":"PATO_0001038"},{"id":"T277","span":{"begin":2145,"end":2150},"obj":"PATO_0001038"},{"id":"T278","span":{"begin":2190,"end":2195},"obj":"PATO_0001038"},{"id":"T279","span":{"begin":2248,"end":2253},"obj":"PATO_0001038"},{"id":"T280","span":{"begin":2299,"end":2304},"obj":"PATO_0001038"},{"id":"T281","span":{"begin":1116,"end":1121},"obj":"PATO_0001470"},{"id":"T282","span":{"begin":2145,"end":2150},"obj":"PATO_0001470"},{"id":"T283","span":{"begin":2190,"end":2195},"obj":"PATO_0001470"},{"id":"T284","span":{"begin":2248,"end":2253},"obj":"PATO_0001470"},{"id":"T285","span":{"begin":2299,"end":2304},"obj":"PATO_0001470"},{"id":"T286","span":{"begin":1157,"end":1166},"obj":"PATO_0000470"},{"id":"T287","span":{"begin":1270,"end":1279},"obj":"PATO_0000470"},{"id":"T288","span":{"begin":1895,"end":1901},"obj":"PATO_0000128"},{"id":"T289","span":{"begin":2073,"end":2079},"obj":"PATO_0001309"},{"id":"T290","span":{"begin":2129,"end":2138},"obj":"CHEBI_6931"},{"id":"T291","span":{"begin":2162,"end":2174},"obj":"CHEBI_25858"},{"id":"T292","span":{"begin":2269,"end":2281},"obj":"CHEBI_34665"},{"id":"T293","span":{"begin":2657,"end":2665},"obj":"PATO_0001727"}],"attributes":[{"subj":"T294","pred":"source","obj":"NEUROSES"},{"subj":"T235","pred":"source","obj":"NEUROSES"},{"subj":"T236","pred":"source","obj":"NEUROSES"},{"subj":"T237","pred":"source","obj":"NEUROSES"},{"subj":"T238","pred":"source","obj":"NEUROSES"},{"subj":"T239","pred":"source","obj":"NEUROSES"},{"subj":"T240","pred":"source","obj":"NEUROSES"},{"subj":"T241","pred":"source","obj":"NEUROSES"},{"subj":"T242","pred":"source","obj":"NEUROSES"},{"subj":"T243","pred":"source","obj":"NEUROSES"},{"subj":"T244","pred":"source","obj":"NEUROSES"},{"subj":"T245","pred":"source","obj":"NEUROSES"},{"subj":"T246","pred":"source","obj":"NEUROSES"},{"subj":"T247","pred":"source","obj":"NEUROSES"},{"subj":"T248","pred":"source","obj":"NEUROSES"},{"subj":"T249","pred":"source","obj":"NEUROSES"},{"subj":"T250","pred":"source","obj":"NEUROSES"},{"subj":"T251","pred":"source","obj":"NEUROSES"},{"subj":"T252","pred":"source","obj":"NEUROSES"},{"subj":"T253","pred":"source","obj":"NEUROSES"},{"subj":"T254","pred":"source","obj":"NEUROSES"},{"subj":"T255","pred":"source","obj":"NEUROSES"},{"subj":"T256","pred":"source","obj":"NEUROSES"},{"subj":"T257","pred":"source","obj":"NEUROSES"},{"subj":"T258","pred":"source","obj":"NEUROSES"},{"subj":"T259","pred":"source","obj":"NEUROSES"},{"subj":"T260","pred":"source","obj":"NEUROSES"},{"subj":"T261","pred":"source","obj":"NEUROSES"},{"subj":"T262","pred":"source","obj":"NEUROSES"},{"subj":"T263","pred":"source","obj":"NEUROSES"},{"subj":"T264","pred":"source","obj":"NEUROSES"},{"subj":"T265","pred":"source","obj":"NEUROSES"},{"subj":"T266","pred":"source","obj":"NEUROSES"},{"subj":"T267","pred":"source","obj":"NEUROSES"},{"subj":"T268","pred":"source","obj":"NEUROSES"},{"subj":"T269","pred":"source","obj":"NEUROSES"},{"subj":"T270","pred":"source","obj":"NEUROSES"},{"subj":"T271","pred":"source","obj":"NEUROSES"},{"subj":"T272","pred":"source","obj":"NEUROSES"},{"subj":"T273","pred":"source","obj":"NEUROSES"},{"subj":"T274","pred":"source","obj":"NEUROSES"},{"subj":"T275","pred":"source","obj":"NEUROSES"},{"subj":"T276","pred":"source","obj":"NEUROSES"},{"subj":"T277","pred":"source","obj":"NEUROSES"},{"subj":"T278","pred":"source","obj":"NEUROSES"},{"subj":"T279","pred":"source","obj":"NEUROSES"},{"subj":"T280","pred":"source","obj":"NEUROSES"},{"subj":"T281","pred":"source","obj":"NEUROSES"},{"subj":"T282","pred":"source","obj":"NEUROSES"},{"subj":"T283","pred":"source","obj":"NEUROSES"},{"subj":"T284","pred":"source","obj":"NEUROSES"},{"subj":"T285","pred":"source","obj":"NEUROSES"},{"subj":"T286","pred":"source","obj":"NEUROSES"},{"subj":"T287","pred":"source","obj":"NEUROSES"},{"subj":"T288","pred":"source","obj":"NEUROSES"},{"subj":"T289","pred":"source","obj":"NEUROSES"},{"subj":"T290","pred":"source","obj":"NEUROSES"},{"subj":"T291","pred":"source","obj":"NEUROSES"},{"subj":"T292","pred":"source","obj":"NEUROSES"},{"subj":"T293","pred":"source","obj":"NEUROSES"}]},{"project":"2_test","denotations":[{"id":"25093031-23470874-29486337","span":{"begin":330,"end":332},"obj":"23470874"},{"id":"25093031-15328251-29486338","span":{"begin":562,"end":564},"obj":"15328251"},{"id":"25093031-15900287-29486339","span":{"begin":2042,"end":2044},"obj":"15900287"}],"attributes":[{"subj":"25093031-23470874-29486337","pred":"source","obj":"2_test"},{"subj":"25093031-15328251-29486338","pred":"source","obj":"2_test"},{"subj":"25093031-15900287-29486339","pred":"source","obj":"2_test"}]},{"project":"MyTest","denotations":[{"id":"25093031-23470874-29486337","span":{"begin":330,"end":332},"obj":"23470874"},{"id":"25093031-15328251-29486338","span":{"begin":562,"end":564},"obj":"15328251"},{"id":"25093031-15900287-29486339","span":{"begin":2042,"end":2044},"obj":"15900287"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"25093031-23470874-29486337","pred":"source","obj":"MyTest"},{"subj":"25093031-15328251-29486338","pred":"source","obj":"MyTest"},{"subj":"25093031-15900287-29486339","pred":"source","obj":"MyTest"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"NEUROSES","color":"#ec93a9","default":true},{"id":"2_test","color":"#93c3ec"},{"id":"MyTest","color":"#ddec93"}]}]}}