red blood cell (RBC) partitioning can be considered to be specific case of protein binding. Certain therapeutic compounds have a high degree of affinity for the red blood cell fraction of whole blood and so hace large RBC-to-plasma concentration ratios. In the design of pharmacokinetics studies, compounds with high partition ratios will likely require assaying whole blood rather than plasma to accurately measure drug concentrations in vivo. also, when assessinf the pharmacokinetic profile of a drug, if it necessary to calculate the clearance of a drug as a function of blood flow to a particular organ, the total blood concentration and therefore the RBC-to-plama partition ratio must be know. finally identification of compounds with high RBC-to-plasma ratios is useful at the lead optimization stage as an indicator of potential problems with red blood cell accumulation and hematotoxicity, particularly, for compounds which are intended for long-term use.
Protocol
| Matrix | Mouse or human blood |
| Test concentration | 1µM |
| Test temperature | 37°C |
| Incubation time | 1h |
| Controls | methazolamide and verapamil |
| Analysis method | LCMS-MS |
| Data delivery | Blood partition coefficient |
| Replicate | 2 |
Data
| Compound | Blood partitioning |
| Verapamil | 1 % |
| Methazolamide | 29 % |
| imipramine | 1,5 % |
Blood partitioning measured at 37°C in mouse whole blood.