Potential pharmacokinetic interactions affecting antitumor drug disposition in cancer patients.
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.
Lemachatti
Jihane
J
Pharmacy, Hôpital Hautepierre, avenue Molière, 67000 Strasbourg, France.
Levêque
Dominique
D
Beretz
Laurence
L
Bergerat
Jean Pierre
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D015897:Comorbidity; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D055815:Young Adult
D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System