Altered protein binding of disopyramide in plasma from patients with cancer and with inflammatory disease.
Protein binding of disopyramide (D) was studied in eight patients with cancer, seven with inflammatory diseases, and seven healthy subjects. Plasma samples containing concentrations of 0.2-12.0 micrograms/ml were ultrafiltered, and the free fractions were measured with fluorescence polarization immunoassay. The mean free fractions at D concentrations ranging from 1.0 to 6.0 micrograms/ml were significantly less in patients with cancer (p less than 0.01) and those with inflammatory diseases (p less than 0.05) than in healthy subjects. Patients with cancer had a greater (p less than 0.05) D binding than those with inflammatory diseases. A multiple regression analysis revealed a significant contribution of plasma alpha 1-acid glycoprotein (AAG) (r = -0.79, p less than 0.01), but not of albumin (r = -0.096), to the overall variability in D binding at 3.0 micrograms/ml. The mean capacity constant in the two patient groups was similar, but significantly (p less than 0.01) greater than in the healthy group. Nonspecific D binding was greater in cancer patients (p less than 0.01) compared to the other two groups. Our results suggest that (a) therapeutic range of D measured as total drug concentration in patients with cancer and with inflammatory diseases would be greater than previously thought, and (b) unidentified component(s) (other than AAG and albumin) might contribute to the greater D binding in cancer patients compared to other study groups.
Echizen
H
H
Division of Gastroenterology, National Medical Center, Tokyo, Japan.
Saima
S
S
Umeda
N
N
Ishizaki
T
T
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism*; D004206:Disopyramide / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*; D009961:Orosomucoid / Q000032:analysis; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis
D001798:Blood Proteins; D009961:Orosomucoid; D012709:Serum Albumin; D004206:Disopyramide