Distribution of tetracycline in red blood cells.

The distribution of tetracycline into human red blood cells was studied in vitro at 37 degrees. The drug was taken up rapidly by the cells, and its distribution equilibrium was reached after approximately 10 min of incubation. The steady-state distribution ratio of the drug between the red cells and extracellular fluid of 0.9% NaCl solution was 2.84, while the distribution ratio between the cells and the plasma solution was 0.9. The reduced cellular uptake in plasma was due to binding of the drug to plasma components. Calcium ions in plasma appeared to reduce tetracycline uptake by the red cells. The red cell distribution of tetracycline in dogs was in close agreement with the in vitro data using the washed human red cells. A dog suffering from severe hypoalbuminemia showed greater uptake of the drug by the erythrocytes, while a normal healthy dog exhibited the red cell-plasma distribution ratio of 0.98. The release rate of tetracycline from the preloaded cells into normal saline solution indicated that the release was directly proportional to the cellular concentration of the drug; the first-order release rate was approximately 1.38 hr-1.