Drug-drug interactions in pediatric oncology patients.

BACKGROUND: Drug-drug interactions (DDIs) can negatively affect pharmacotherapy. However, pediatric DDI studies are scarce. We undertook an exploratory study to investigate prevalence and clinical relevance of DDIs between cytostatic and noncytostatic drugs in outpatient pediatric oncology patients. PROCEDURE: After informed consent and inclusion, the following information was collected: currently prescribed noncytostatic and cytostatic drugs, comorbidities, and use of over-the-counter (OTC) drugs, complementary and alternative medicines (CAMs), and dietary supplements. All medication was screened for DDIs according to two databases: Micromedex® Solutions and the Dutch drug database G-Standard. The researcher presented DDIs with an associated potential for adverse outcome and a proposal for intervention to three independent experts. If the experts considered a DDI to be potentially clinically relevant and requiring intervention, the physician was notified. RESULTS: Seventy-three patients were included (median age 8.9 years). A total of 67 different DDIs were counted (66 in Micromedex® Solutions, 14 in G-Standard, and 13 DDIs in both databases). The medication reviews resulted in 35 interventions related to 11 different DDIs. The majority of DDIs concerned noncytostatic drugs (25/35) and one third occurred between cytostatic and noncytostatic drugs (10/35). The use of QTc-interval-prolonging drugs resulted in one intervention. The use of OTC drugs, CAM, or dietary supplements did not lead to DDIs. CONCLUSIONS: This study resulted in a selection of 11 potentially clinically relevant DDIs for 73 outpatients in our pediatric oncology department. Interventions were formulated in close collaboration between physicians and clinical pharmacists. Future research should focus on assessing DDIs concerning QTc-interval prolongation.

Pitfalls of the application of microdialysis in clinical oncology: controversial findings with docetaxel.

Microdialysis is a novel and minimally invasive sampling technique, based on the diffusion of analytes from the interstitial compartment through a semi-permeable membrane, and enables direct assessment of tissue disposition and penetration of drugs. Variable antitumor responses may be associated with differences in tumor vascularity, capillary permeability or tumor interstitial pressure resulting in variable delivery of anticancer agents. In preparation of pharmacokinetic studies, aimed at measuring docetaxel concentrations in healthy and malignant tissues in vivo, in pre-clinical as well as clinical studies, in vitro recovery experiments were performed. In contrast to published data, the recovery experiments suggest that docetaxel has a very low recovery as a result of non-specific binding to currently available microdialysis catheters. Here we discuss our findings with docetaxel in a historical perspective and we report on our experience using polysorbate 80 to eliminate the non-specific binding and its effects on the recovery of docetaxel.

Potential for improvement of docetaxel-based chemotherapy: a pharmacological review.

Since the introduction of docetaxel, research has focused on various approaches to overcome treatment limitations and improve outcome. This review discusses the pharmacological attempts at treatment optimisation, which include reducing interindividual pharmacokinetic and pharmacodynamic variability, optimising schedule, route of administration, reversing drug resistance and the development of structurally related second-generation taxanes.