Cyclooxygenase inhibition with ibuprofen: effect on biodistribution of perflubron emulsions in mice with mammary tumor.
The biodistribution of Perflubron (perfluorocytylbromide, PFOB) was studied by infusing 10 or 3 g/Kg doses of 90% and 100% w/v emulsions into Balb C mice with and without malignant mammary tumor implants. PFOB concentrations were measured in blood, liver, spleen, lung and tumor, and X-rays were taken 48 hours after infusion. Ibuprofen (IBU) was given intraperitoneally 10 mg/Kg dialy for 3 days to study the effects of cyclooxygenase blockade. The results showed that the blood [PFOB] in tumor-bearing mice (TBM) was only 3.6% of that measured in normal mice (NM), and the liver [PFOB] was increased by 59%. The lung [PFOB] increase with IBU therapy in NM was highly significant. IBU therapy resulted in a 98% and 468% increase in blood [PFOB] in normal and TBM, respectively. Smaller but statistically significant changes occurred in blood [PFOB] with saline and sham injections. Tumor [PFOB] was lower by 17% (P = .028) in mice treated with IBU. Smaller decreases were seen with saline and sham injections but did not achieve statistical significance. In conclusion, the presence of this malignant tumor resulted in changes that might influence the usefulness of PFOB as a contrast agent and as an adjuvant for radiation and chemotherapy. This study shows that cyclooxygenase inhibition significantly modified the pharmacodynamics of PFOB emulsions in blood, tumor and lung. The changes seen in the saline placebo and sham category were attributed to stress from procedures.
Long
D M
DM
Department of Radiology, University of California, San Diego 92103.
Vasquez
F
F
Witt
B L
BL
Escobar
J A
JA
Long
R A
RA
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D004655:Emulsions; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006842:Hydrocarbons, Brominated; D007052:Ibuprofen / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects
D003287:Contrast Media; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D011838:Radiation-Sensitizing Agents; C003072:perflubron; D007052:Ibuprofen