The pharmacologic effects of recombinant, human colony-stimulating factors and their modulation by theophylline.
OBJECTIVE
To investigate the effect of colony-stimulating factors (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).


METHODS
Open-label, prospective study.


METHODS
The bone marrow transplant unit of a tertiary university teaching hospital.


METHODS
Thirty-seven women with breast cancer (28 phase I, 9 phase II).


METHODS
Patients received aminophylline 0.58 mg/kg either as a 30-minute intravenous infusion before receiving recombinant CSFs or after several days of CSF therapy, just before high-dose chemotherapy (phase I) or as a continuous intravenous infusion after bone marrow transplantation (phase II).


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 interleukin 6.


CONCLUSIONS
Administration of CSFs before autologous bone marrow transplantation for priming progenitor cells may alter drug metabolism. Studies should be conducted to evaluate the potential effects of CSFs on the disposition of chemotherapeutic agents.
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
W P
WP
Petros
G L
GL
Rosner
J
J
Rabinowitz
C J
CJ
Gilbert
D
D
Coniglio
J J
JJ
Vredenburgh
M
M
Ross
W P
WP
Peters
D000328:Adult; D000628:Aminophylline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins
D016207:Cytokines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000628:Aminophylline; D016178:Granulocyte-Macrophage Colony-Stimulating Factor