Stockler R M, Morin D E, Lantz R K, Hurley W L, Constable P D
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
J Vet Pharmacol Ther. 2009 Aug;32(4):345-52. doi: 10.1111/j.1365-2885.2008.01048.x.
Clinical mastitis in dairy cows is commonly treated with intramammary (IMM) antimicrobial agents. Pharmacokinetic data are used to design treatment regimens and determine withholding times. In some pharmacokinetic studies, investigators measure antimicrobial concentrations in foremilk, whereas in others, they use bucket milk or do not specify the milk fraction sampled. Our objective was to compare antimicrobial concentrations in foremilk, bucket milk, and strippings after IMM treatment of six healthy Holsteins. One mammary gland/cow was infused with 200 mg of cephapirin (CEPH) after each of the two milkings, using different milking frequencies and treatment intervals in a randomized crossover design. Treated glands were sampled at the first milking following each infusion. Antimicrobial concentrations in milk were measured using HPLC/MS/MS. CEPH concentration was higher in foremilk (geometric mean 44.2 microg/mL) than in bucket milk (15.7 microg/mL) or strippings (18.5 microg/mL), as it was true for desacetylcephapirin (DAC) (59.5, 23.0, and 30.2 microg/mL, respectively). This finding, which was based on milk samples collected at the first milking after IMM infusion, suggests that pharmacokinetic data based on drug concentrations in foremilk may be misleading. Strippings were more representative of bucket milk than foremilk. The relationship between milk fraction and antimicrobial concentration should be investigated for other IMM antimicrobial agents. Meanwhile, it is essential that pharmacokinetic and residue studies report the fraction of milk that was analyzed.
奶牛临床型乳腺炎通常采用乳房内（IMM）抗菌剂进行治疗。药代动力学数据用于设计治疗方案并确定停药期。在一些药代动力学研究中，研究人员测量前乳中的抗菌剂浓度，而在其他研究中，他们使用桶奶或未指明所采集的乳的部分。我们的目的是比较对6头健康荷斯坦奶牛进行IMM治疗后前乳、桶奶和挤奶余液中的抗菌剂浓度。采用随机交叉设计，在两次挤奶后，对每头奶牛的一个乳腺注入200 mg头孢匹林（CEPH），使用不同的挤奶频率和治疗间隔。在每次注入后的第一次挤奶时对处理过的乳腺进行采样。使用高效液相色谱/串联质谱法测量乳中的抗菌剂浓度。前乳中的CEPH浓度（几何平均值44.2 μg/mL）高于桶奶（15.7 μg/mL）或挤奶余液（18.5 μg/mL），去乙酰头孢匹林（DAC）的情况也是如此（分别为59.5、23.0和30.2 μg/mL）。这一基于IMM注入后第一次挤奶时采集的乳样的发现表明，基于前乳中药物浓度的药代动力学数据可能会产生误导。挤奶余液比前乳更能代表桶奶。对于其他IMM抗菌剂，应研究乳的部分与抗菌剂浓度之间的关系。同时，药代动力学和残留研究必须报告所分析的乳的部分。
