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Pharmacokinetics profiles of cyclosporine in rats influence of route of administration and dosage


, : Pharmacokinetics profiles of cyclosporine in rats influence of route of administration and dosage. Transplantation (Baltimore) 40(5): 489-493

This study was performed to determine the influence of different routes of administration and of variable doses of cyclosporine (CsA) on the pharmacokinetics of CsA in the rat. Seven groups of 4 adult female Lewis rats were given CsA once daily for 5 days: group 1:5 mg/kg of CsA p.o. (by gavage); group 2: 10 mg/kg of CsA p.o.; Group 3: 5 mg/kg of CsA i.m.; group 4: 10 mg/kg of CsA i.m.; Group 5: 5 mg/kg of CsA s.c.; group 6: 10 mg/kg of CsA s.c., group 7: 10 mg/kg CsA i.p. CsA plasma levels were determined by RIA at 0, 2, 4, 6, 8 and 24 hr on days 1 and 4. Ease of administration was greatest in the s.c. groups (3 and 4), in which no anesthesia, no restraining device, and no special skills were required. Peak CsA levels varied greatly from group to group, as did trough levels and CsA bioavailability, as determined by the total area under the plasma CsA concentration-time curve. All groups exhibited great variation of CsA plasma level in the 24-hr period following administration, except group 3, in which the peak-to-trough difference was only 26.8% of peak level, as opposed to values over 60% in all other groups. We conclude that: (1) CsA may be administered to rats through different routes to achieve adequate plasma levels; (2) the route and dosage will greatly influence the pharmacokinetic profile of CsA; and (3) the SC route, in addition to being the easiest, provides reproducible and steady CsA plasma levels, with little variation over a 24-hr period.

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PMID: 3877356


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