MacKay Evelyn E, Washburn Kevin E, Padgett Ashley L, Fajt Virginia R, Lo Chih-Ping, Mays Travis P, Washburn Shannon E
Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas.
Department of Veterinary Physiology and Pharmacology, Michael E. DeBakey Institute, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas.
J Vet Pharmacol Ther. 2019 Jul;42(4):373-379. doi: 10.1111/jvp.12744. Epub 2019 Jan 17.
Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time-course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus.
大环内酯类药物是重要的抗菌剂,常用于人类和兽医学中治疗孕妇和怀孕家畜。它们可能有助于控制传染性绵羊流产,这种流产对经济、动物健康和人类健康都有影响。在本研究中,在妊娠115(±2)天时,通过手术将导管放置在怀孕母羊的胎儿血管和羊膜中。给母羊皮下注射单剂量2.5mg/kg的图拉霉素,并在给药后4、8、12、24、36、48、72、144和288小时测定胎儿血浆、母体血浆和羊水中药物浓度。使用非房室分析估计母体血浆中的药代动力学参数,这些参数与先前在非怀孕母羊中报道的参数相似。图拉霉素存在于胎儿血浆和羊水中,表明其对这些部位的生物体具有治疗潜力,尽管其浓度低于母体血浆中的浓度。胎儿体内药物浓度的时间进程与母羊有很大不同,血浆浓度在4小时时达到平台期,并在剩余的采样期(288小时)内保持在该浓度,这引发了关于图拉霉素如何被胎儿转运、代谢和消除的疑问。