THE PHARMACOLOGICAL EFFECTS OF RECOMBINANT, HUMAN COLONY-STIMULATING FACTORS AND THEIR MODULATION BY THEOPHYLLINE

Study Objectives. To investigate the effect of colony-stimulating fact ors (CSFs) on drug metabolism using theophylline as a substrate (phase I), and to evaluate the influence of theophylline on endogenous serum cytokine concentrations (phase II). Design. Open-label, prospective s tudy. Setting, The bone marrow transplant unit of a tertiary universit y teaching hospital. Patients. Thirty-seven women with breast cancer ( 28 phase I, 9 phase II). Interventions, Patients received aminophyllin e 0.58 mg/kg either as a 30-minute intravenous infusion before receivi ng recombinant CSFs or after several days of CSF therapy, just before high-dose chemotherapy (phase I) or as a continuous intravenous infusi on after bone marrow transplantation (Phase II). Measurements and Main Results. Clearance of theophylline was significantly higher after CSF administration (0.76 vs 0.99 ml/min/kg, p=0.019). Continuous infusion of aminophylline resulted in elevations of serum macrophage-CSF and i nterleukin-6. Conclusions. Administration of CSFs before autologous bo ne marrow transplantation for priming progenitor cells may alter drug metabolism. Studies should be conducted to evaluate the potential effe cts of CSFs on the disposition of chemotherapeutic agents.