Kendall Lon V, Hansen Ryan J, Dorsey Kathryn, Kang Sooah, Lunghofer Paul J, Gustafson Daniel L
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
J Am Assoc Lab Anim Sci. 2014 Sep;53(5):478-84.
Buprenorphine and carprofen, 2 of the most commonly used analgesics in mice, must be administered every 8 to 12 h to provide sustained analgesia. Sustained-release (SR) formulations of analgesics maintain plasma levels that should be sufficient to provide sustained analgesia yet require less frequent dosing and thus less handling of and stress to the animals. The pharmacokinetics of SR formulations of buprenorphine (Bup-SR), butorphanol (Butp-SR), fentanyl (Fent-SR), carprofen (Carp-SR), and meloxicam (Melox-SR) were evaluated in mice over 72 h and compared with those of traditional, nonSR formulations. Bup-SR provided plasma drug levels greater than the therapeutic level for the first 24 to 48 h after administration, but plasma levels of Bup-HCl fell below the therapeutic level by 4 h. Fent-SR maintained plasma levels greater than reported therapeutic levels for 12 h. Therapeutic levels of the remaining drugs are unknown, but Carp-SR provided plasma drug levels similar to those of Carp for the first 24 h after administration, whereas Melox-SR had greater plasma levels than did Melox for the first 8 h. Butp-SR provided detectable plasma drug levels for the first 24 h, with a dramatic decrease over the first 4 h. These results indicate that Bup-SR provides a stable plasma drug level adequate for analgesia for 24 to 48 h after administration, whereas Carp-SR, Melox-SR, Fent-SR, and Butp-SR would require additional doses to provide analgesic plasma levels beyond 24 h in mice.
丁丙诺啡和卡洛芬是小鼠最常用的两种镇痛药，必须每8至12小时给药一次以提供持续镇痛。镇痛药的缓释（SR）制剂可维持血浆水平，该水平应足以提供持续镇痛，但给药频率较低，因此对动物的处理和应激也较少。在72小时内对小鼠评估了丁丙诺啡（Bup-SR）、布托啡诺（Butp-SR）、芬太尼（Fent-SR）、卡洛芬（Carp-SR）和美洛昔康（Melox-SR）的SR制剂的药代动力学，并与传统的非SR制剂进行了比较。给药后最初24至48小时，Bup-SR的血浆药物水平高于治疗水平，但盐酸丁丙诺啡的血浆水平在4小时时降至治疗水平以下。Fent-SR维持血浆水平高于报道的治疗水平达12小时。其余药物的治疗水平未知，但给药后最初24小时，Carp-SR的血浆药物水平与卡洛芬相似，而Melox-SR在最初8小时的血浆水平高于美洛昔康。Butp-SR在最初24小时可检测到血浆药物水平，在最初4小时内急剧下降。这些结果表明，Bup-SR给药后24至48小时可提供足以镇痛的稳定血浆药物水平，而Carp-SR、Melox-SR、Fent-SR和Butp-SR在小鼠中需要额外给药以提供超过24小时的镇痛血浆水平。
