Bioavailability assessment of cyclosporine in the rat. Influence of route of administration.

Systemic availability determines the net loss of drug through poor dosage form design, incomplete absorption, first-pass metabolism, and other reasons for drug destruction. The present study demonstrates the wide variability in assessment of single-dose bioavailability of cyclosporine A (CSA) based on the route of parenteral administration. Rats were administered CSA (10 or 25 mg/kg) orally or via the ip route, and the systemic availability was estimated from drug administered via the penile, femoral, or jugular route. CSA delivered via the jugular vein resulted in a significantly greater AUC (22,253 +/- 8,087 ng-hr/ml), compared to the AUC estimated after femoral, penile, or ip routes (11,919 +/- 1,760, 9,718 +/- 1,113, and 4,233 +/- 1,741 ng-hr/ml, respectively; p less than 0.05). There were no differences in elimination rate constants between groups. However, there was significant delay observed in peak concentration following both femoral vein and ip administration, similar to oral absorption. The bioavailability estimated for each oral dose did not significantly differ within groups but was widely variable, depending upon the intravascular standard used in the equation. The present data illustrate the specificity of route of nonenteral administration in the assessment of systemic availability in the rat model.