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  • Title: Marked interspecies differences between humans and pigs in cyclosporine and prednisolone disposition.
    Author: Frey BM, Sieber M, Mettler D, Gänger H, Frey FJ.
    Journal: Drug Metab Dispos; 1988; 16(2):285-9. PubMed ID: 2898348.
    Abstract:
    Pigs have been used extensively in various transplantation protocols. Immunosuppressive therapy is usually performed by steroids and cyclosporine A (CyA). For rational dosage of these xenobiotics, their pharmacokinetics should be characterized. Therefore, we investigated the kinetics of prednisolone, an immunobiologically active steroid, after oral and iv administration, and of CyA, after oral and iv dosing, in seven pigs and compared these results with those obtained in 20 renal transplant patients. The mean area under the blood concentration versus time curve of CyA (HPLC measurements) was lower in pigs than in humans after oral (67 +/- 31 micrograms/ml x min vs. 296 +/- 101 micrograms/ml x min) and after iv (358 +/- 71 micrograms/ml x min vs. 858 +/- 292 micrograms/ml x min) doses of CyA. Compared to humans, pigs had lower concentrations of total prednisolone--assessed by HPLC--after oral prednisone (7.1 +/- 4.3 micrograms/ml x min vs. 297.9 +/- 75.6 micrograms/ml x min) and after iv prednisolone (26.8 +/- 9.5 micrograms/ml x min vs. 373.3 +/- 77.7 micrograms/ml x min). The plasma concentrations of both agents, lower in pigs than in humans, were attributable to an increased volume of distribution, an increased clearance, and more of a diminished systemic availability in pigs than in humans. Thus, to obtain the same target concentrations of CyA and prednisolone in both species, pigs require about 2 to 4 times higher iv or oral doses of CyA and 10 to 30 times higher iv or oral doses of steroids.
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