Significant inhibitory impact of dibenzyl trisulfide and extracts of Petiveria alliacea on the activities of major drug-metabolizing enzymes in vitro: An assessment of the potential for medicinal plant-drug interactions.

Dibenzyl trisulfide (DTS) is the major active ingredient expressed in Petiveria alliacea L., a shrub widely used for a range of conditions, such as, arthritis, asthma and cancer. Given its use alone and concomitantly with prescription medicines, we undertook to investigate its impact on the activities of important drug metabolizing enzymes, the cytochromes P450 (CYP), a key family of enzymes involved in many adverse drug reactions. DTS and seven standardized extracts from the plant were assessed for their impact on the activities of CYPs 1A2, 2C19, 2C9, 2D6 and 3A4 on a fluorometric assay. DTS revealed significant impact against the activities of CYPs 1A2, 2C19 and 3A4 with IC50 values of 1.9, 4.0 and 3.2µM, respectively, which are equivalent to known standard inhibitors of these enzymes (furafylline, and tranylcypromine), and the most potent interaction with CYP1A2 displayed irreversible enzyme kinetics. The root extract, drawn with 96% ethanol (containing 2.4% DTS), displayed IC50 values of 5.6, 3.9 and 4.2µg/mL respectively, against the same isoforms, CYPs 1A2, 2C19 and 3A4. These investigations identify DTS as a valuable CYP inhibitor and P. alliacea as a candidate plant worthy of clinical trials to confirm the conclusions that extracts yielding high DTS may lead to clinically relevant drug interactions, whilst extracts yielding low levels of DTS, such as aqueous extracts, are unlikely to cause adverse herb-drug interactions.

Informal consultation at a teaching hospital infectious diseases department.

INTRODUCTION: Informal consultations for advice in the infectious diseases department (IDD) induce a significant workload for physicians. Our aim was to retrospectively quantify and describe this activity in our institution. METHOD: The data was obtained from files documented and faxed by physicians from October 2009 to May 2012. One thousand nine hundred and seventy-two files were included. The file was faxed to the IDD specialist, analyzed, then a telephone conversation allowed making precisions, and the documented form was faxed back. RESULTS: The requests for advice concerned 39% of female and 61% of male patients with a mean age of 64±21 years. Twenty-nine percent of requests came from surgical departments and 71% from medical departments (P<0.01). The departments most frequently concerned were cardiology (10%), gastro-enterology (10%) and cardiovascular surgery (9.7%). The most frequent infections were urogenital (19%), osteoarticular (14%), and cardiovascular (11%). Forty-nine percent were considered as nosocomial and 25.3% were bacteremic. The requests concerned diagnostic aid in 16.2% of cases and therapeutic issues in 95.6%. The IDD specialist made therapeutic recommendation in 96.5% of cases and gave diagnostic advice in 43.7%. Treatment modification was suggested in 38.5% of cases. Twenty-two percent of consultations required a second one. CONCLUSION: This study documented the importance of antibiotic changes among medical and surgical units, the increasing need of these units to be helped, and also the complexity of the medical cases, all requiring the advice of an ID specialist. Our fax-phone-fax procedure seems to prevent the bias associated with informal consultations by phone, which is the most commonly used in other institutions.