Yanyan Cui

Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans.

Phytochemical‐mediated modulation of cytochrome P450 (CYP) activity may underlie many herb‐drug interactions. Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of St Johns wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity.

Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba.

ObjectivesElderly patients are more likely to ingest prescription medications concurrently with botanical supplements, and may therefore be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. In this study, single timepoint, phenotypic metabolic ratios were used to determine whether long-term supplementation of St John’s wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly subjects.MethodsTwelve healthy volunteers between the ages of 60 and 76 years (mean age 67 years) were randomly assigned to receive each botanical supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and debrisoquine urinary recovery ratios (8-hour), respectively. The content of purported ‘active’ phytochemicals was determined for each supplement.ResultsComparisons of pre- and post-St John’s wort phenotypic ratios revealed significant induction of CYP3A4 (≈140%) and CYP2E1 activity (≈28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (≈7%) did not appear to be clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity.ConclusionsElderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John’s wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared with earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly.

Determination of hyperforin in human plasma using solid-phase extraction and high-performance liquid chromatography with ultraviolet detection

Hyperforin is one of the most important active components in St. Johns wort (Hypericum perforatum), a botanical dietary supplement used as an alternative treatment modality for mild to moderate depression. A solid-phase extraction (SPE) and an isocratic high-performance liquid chromatography (HPLC) analysis with ultraviolet (UV) detection were developed to determine hyperforin in human plasma samples. Benzo[k]fluoranthene was used as an internal standard. The absolute recovery for hyperforin was more than 89% for plasma concentrations ranging from 25 to 500 ng/ml. The linearity of calibration curves, inter-day and intra-day relative standard deviations were investigated. The limit of detection (LOD) of hyperforin was 4 ng/ml in plasma and the limit of quantitation (LOQ) was 10 ng/ml. Hyperforin concentrations in human plasma following St. Johns wort administration were analyzed. The result suggests that this method is rapid, sensitive, reproducible and capable of quantitative analysis of hyperforin plasma concentrations.