Anti-CYP3A4 polyclonal antibody

Flavonoids are abundant polyphenols in nature. They are extensively biotransformed in enterocytes and hepatocytes, where conjugated (methyl, sulfate, and glucuronide) metabolites are formed. However, bacterial microflora in the human intestines also metabolize flavonoids, resulting in the production of smaller phenolic fragments (e.g., hydroxybenzoic, hydroxyacetic and hydroxycinnamic acids, and hydroxybenzenes). Despite the fact that several colonic metabolites appear in the circulation at high concentrations, we have only limited information regarding their pharmacodynamic effects and pharmacokinetic interactions. Therefore, in this in vitro study, we investigated the interactions of 24 microbial flavonoid metabolites with human serum albumin and cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes. Our results demonstrated that some metabolites (e.g., 2,4-dihydroxyacetophenone, pyrogallol, O-desmethylangolensin, and 2-hydroxy-4-methoxybenzoic acid) form stable complexes with albumin. However, the compounds tested did not considerably displace Site I and II marker drugs from albumin. All CYP isoforms examined were significantly inhibited by O-desmethylangolensin; nevertheless, only its effect on CYP2C9 seems to be relevant. Furthermore, resorcinol and phloroglucinol showed strong inhibitory effects on CYP3A4. Our results demonstrate that, besides flavonoid aglycones and their conjugated derivatives, some colonic metabolites are also able to interact with proteins involved in the pharmacokinetics of drugs.

Background The potential for clinically significant drug interactions (CSDIs) for patients taking ritonavir and cobicistat is high because of their powerful pharmacokinetic effect on the cytochrome P450 (CYP) enzyme system, most notably their inhibitory effect on CYP3A4. Aims An audit was conducted to measure and correct for patients exposed to potentially dangerous drug interactions. Methods Two hundred individuals attending a regional specialist human immunodeficiency virus (HIV) clinic between June and September 2014 who were receiving the pharmacokinetic enhancers ritonavir or cobicistat were interviewed to determine a medication history including medications prescribed by their general practitioner (GP), over-the-counter (OTC) medicines, herbal remedies and recreational drugs. Results Of the 200 patients interviewed, patients were aged 23-76 years (median age was 41.5), 64% were female and 173 reported taking a co-medication. Sixty-six (33%) were taking a medication or medications which had no significant drug interaction associated with them. One hundred and seven (54%) were taking one or more medications with a CSDI which could require a dose adjustment, close monitoring or an absolute contraindication. Only 27% of these co-medications were identified in the normal course of an outpatient visit outside of the audit. Conclusion A detailed medication history is often lacking at routine HIV follow-up visits. There is a significant risk of CSDIs in this cohort. Awareness of physicians and pharmacists needs to be raised. Implementation of several innovative strategies to capture the most accurate medication histories and avoid drug toxicities now employed in this cohort is also discussed here.