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Tissue distribution of cyclosporine A in the mouse: a clue to toxicity?

Four groups of three C57/BL6J mice were each given a single i.p. injection of Cyclosporine A (CYA) 3 mg/kg, containing 3H-CYA with 10 microCi activity. The groups were sacrificed after 5 minutes and at 6, 12 and 24 hours after dosing, respectively. They were immediately flushed with PBS to clear the organs of blood, and the CYA content of blood, kidney, liver, brain, thymus, spleen, heart, lung, muscle and femur were measured by scintillation counting. Hemoglobin concentration in each tissue was negligible. Tissue uptake was expressed as the ratio of activity per gm tissue/activity per ml blood. Organs susceptible to CYA toxicity, e.g., brain, kidney and liver demonstrated retention of CYA relative to blood, as did thymus and spleen. Resistant organs, i.e., heart, lung and muscle did not. The pattern of CYA distribution and clearance corresponded with the known susceptibility of organs to CYA toxicity. CYA kinetics could therefore contribute to its toxicity by means of increased retention and/or accumulation in susceptible organs.