科研之友
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摘要
Long-term oral administration of immunosuppressive agents to transplanted rhesus monkeys (Macaca mulatta) is one of the major challenges in such studies. To avoid the drawbacks of gavage, we tested an alternative method for oral dosing of sirolimus in rhesus monkeys by adding sirolimus, a commonly used immunosuppressant, to gelatin to create drug-containing gelatin 'treats' that our macaques would accept voluntarily. We evaluated the oral bioequivalence of the oral solution and drug-containing gelatin and assayed the whole-blood levels of sirolimus after long-term drug delivery. We found that time to peak concentration but not peak concentration itself or the area under the time-concentration curve differed between the 2 groups. Although the maximal concentration data did not fit the condition of bioequivalence, those for the time concentration curves from 0 to 24 h and from 0 h to infinity did; therefore the extent of sirolimus absorption did not differ significantly between the 2 formulations. The sirolimus levels for long-term drug delivery were equivalent at 2.97 +/- 1.91 ng/mL in the gelatin group and 3.13 +/- 2.03 ng/mL in the solution group. The gelatin dosing technique we describe here is convenient and effective for oral administration of sirolimus in rhesus monkeys and likely can be adapted for other drugs.
