Differential effect of cancer on the serum protein binding to mianserin and imipramine.
Protein binding of mianserin and imipramine in vitro was determined in sera from 10 patients with cancer and from 28 drug-free normal subjects. alpha 1-acid glycoprotein (AAG) concentrations ranged from 0.91 +/- 0.04 g/l in control subjects to 2.17 +/- 0.18 g/l in cancer patients. Albumin concentrations ranged from 55.80 +/- 1.68 g/l in control subjects to 39.71 +/- 4.40 g/l, respectively. Serum samples containing concentrations of 100 ng/ml for mianserin and 500 ng/ml for imipramine were ultrafiltered and the free concentration were measured with scintillation spectrophotometer. The mean free percentage of mianserin was significantly less in patients with cancer (8.70 +/- 0.29% in patients vs 14.30 +/- 0.50% in control subjects P < 0.001). A multiple regression analysis revealed a significant contribution of plasma AAG (r2 = 0.56, P < 0.01), but not of albumin to the overall variability in mianserin binding. No correlation was observed between protein binding of imipramine and AAG concentrations in serum of cancer patients. No significant changes were observed for protein binding of imipramine in cancer patients as compared with control subjects. Our results suggest that for antidepressant (AD) drugs, of which the binding depends on AAG, variability in protein binding could be expected in cancer patients. Thus, in cancer therapy, changes in analgesic doses could be necessary with this kind of antidepressant drug.
Torres
I
I
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
Suárez
E
E
Rodríguez-Sasiain
J M
JM
Aguirre
C
C
Calvo
R
R
D000293:Adolescent; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D006801:Humans; D007099:Imipramine / Q000097:blood*; D008803:Mianserin / Q000097:blood*; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D012044:Regression Analysis; D012709:Serum Albumin / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D001798:Blood Proteins; D009961:Orosomucoid; D012709:Serum Albumin; D008803:Mianserin; D007099:Imipramine