Publications (2)2.9 Total impact
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ABSTRACT: The extent of potential pharmacokinetic drug-drug interactions affecting anticancer agents disposition has not been specifically investigated. The prevalence of this type of interaction in adult ambulatory patients receiving systemic chemotherapy in our institution was examined. The medication list of 200 consecutive cancer patients receiving intravenous chemotherapy was prospectively collected by means of the prescriptions (chemotherapy, supportive care, medications for comorbidities) and a questionnaire (over-the-counter products). Interacting drugs had to have been taken in the previous 7 days. Data concerning the type of cancer and the nature of the comorbidities were also collected. Potential pharmacokinetic drug interactions affecting the activity of the anticancer agent were identified using the guide of drug interactions of the French drug agency (June 2007) and the literature. A total of 200 patients (mean age 60 years; range 17-96 years) entered the study and 73.5% were female. The most common cancer types were breast cancer (41%), non-Hodgkin's lymphomas (17.5%), and gastrointestinal tumors (12.5%). The majority of the patients (58.5%) had a comorbid illness (cardiovascular diseases, hypothyroidism, diabetes, depression). The median number of medications per patient was 4 (range 1-14). All the patients received systemic chemotherapy but 29 (14.5%) also took anticancer drugs at home. Nine potential pharmacokinetic interactions were found in nine patients (frequency: 4.5%; 95% confidence interval: 1.6-7.4%). Most of the interactions (7/9) involved fluconazole that might alter the metabolism of oxazaphosphorines or the elimination of bortezomib and paclitaxel. One association was contraindicated. Five interactions were not associated with a published clinical effect. No interaction with an enzyme or drug transporter inducer (e.g., rifampin, St. John's wort) was encountered. The frequence of potential pharmacokinetic interactions affecting the disposition of antitumor drugs was low in this population of ambulatory adult cancer patients and mostly involved the antifungal agent fluconazole.
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ABSTRACT: Pharmacokinetic drug-drug interactions occur when a drug alters the disposition (absorption, distribution, elimination) of a coadministered agent. Pharmacokinetic interactions may result in the increase or the decrease of plasma drug concentrations. These modifications are variable in intensity but can lead to contraindications of the association. The mechanisms of pharmacokinetic interactions involve drug metabolizing enzymes, drug transporters and orphan nuclear receptors that regulate at the transcriptional level the expression of enzymes and transporters. The increase of drug plasma concentrations is generally related to the inhibition of enzymes and/or drug transport. The decrease of drug concentrations reflects the activation of orphan nuclear receptors by inducers that lead to the increase of the expression of enzymes and drug transporters. Inhibition of drug metabolism or transport is quite immediate (24-48h) while induction is a slower process (7-10 days). Complex situations may be observed with drugs that are both inducers and inhibitors (rifampin, ritonavir). They can cause the decrease and the increase of the exposure of the combined agent depending on the duration of the association.
University of StrasbourgStrasburg, Alsace, France