Potential pharmacokinetic interactions affecting antitumor drug disposition in cancer patients. 2009

Jihane Lemachatti, and Dominique Levêque, and Laurence Beretz, and Jean Pierre Bergerat
Pharmacy, Hôpital Hautepierre, avenue Molière, 67000 Strasbourg, France.

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007037 Hypothyroidism A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction. Central Hypothyroidism,Primary Hypothyroidism,Secondary Hypothyroidism,TSH Deficiency,Thyroid-Stimulating Hormone Deficiency,Central Hypothyroidisms,Deficiency, TSH,Deficiency, Thyroid-Stimulating Hormone,Hormone Deficiency, Thyroid-Stimulating,Hypothyroidism, Central,Hypothyroidism, Primary,Hypothyroidism, Secondary,Hypothyroidisms,Primary Hypothyroidisms,Secondary Hypothyroidisms,TSH Deficiencies,Thyroid Stimulating Hormone Deficiency,Thyroid-Stimulating Hormone Deficiencies
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D002318 Cardiovascular Diseases Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM. Adverse Cardiac Event,Cardiac Events,Major Adverse Cardiac Events,Adverse Cardiac Events,Cardiac Event,Cardiac Event, Adverse,Cardiac Events, Adverse,Cardiovascular Disease,Disease, Cardiovascular,Event, Cardiac
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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