Partitioning of thioridazine and mesoridazine in human blood fractions
Dinovo, E.C.; Pollak, H.; Gottschalk, L.A.
Methods and Findings in Experimental and Clinical Pharmacology 6(3): 143-146
1984
ISSN/ISBN: 0379-0355 PMID: 6748818 Document Number: 228598
The partitioning of 3H-thioridazine and 3H-mesoridazine were solubilized using the New England Nuclear protocol for whole blood solubilization. The plasma fraction was further fractionated into protein bound and free drug by molecular ultrafiltration. All solutions were counted in Biofluor LSC cocktail and corrected for quenching. Greater than 99% of the labeled drug was bound to the red blood cells and plasma protein. For thioridazine, 59% was bound to RBC, 41% was bound to plasma protein and 0.7% is free; for mesoridazine, 63% was bound to RBC, 37% was bound to plasma protein and 0.9% was free. Though substantial overlap was found in the bound percentage for mesoridazine and thioridazine, more mesoridazine bound to RBC than thioridazine (P < 0.01). There was no statistically significant relationship between the amount of drug bound to the RBC or to plasma protein and the percent free drug. Though the total drug concentration was the same (1 mg/ml) the percent free drug was quite variable across subjects by as much as a factor of 3. Since free drug was the pharmacologically active portion and therefore the determinant of clinical response, the reported variation in free drug concentration at the same total blood concentration invalidated the measurements of total serum or plasma drug concentration as predictive of clinical response.