title: Drug-containing gelatin treats as an alternative to gavage for long-term oral administration in rhesus monkeys (Macaca mulatta).
abstract: 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.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.forename: Younan
authors.initials: Y
authors.lastname: Chen
authors.forename: Sirong
authors.initials: S
authors.lastname: He
authors.forename: Chengshi
authors.initials: C
authors.lastname: Wang
authors.forename: Xinli
authors.initials: X
authors.lastname: Li
authors.forename: Jiuming
authors.initials: J
authors.lastname: Zhao
authors.forename: Meimei
authors.initials: M
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005780:Gelatin / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008253:Macaca mulatta; D023421:Models, Animal; D020123:Sirolimus / Q000008:administration & dosage*; D013810:Therapeutic Equivalency; D014180:Transplantation
chemical_list: D007166:Immunosuppressive Agents; D005780:Gelatin; D020123:Sirolimus