McIntyre Alyssa R, Lipman Neil S
Tri-Institutional Training Program in Laboratory Animal Medicine and Science, New York, NY, USA.
J Am Assoc Lab Anim Sci. 2007 Sep;46(5):26-32.
We assessed the concentrations of 2 antibiotic combinations, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole when compounded in reverse osmosis [RO] (pH 6.0), tap (pH 6.7), and acidified water (pH 2.6) over 7 d, and pre- and post-pelleting, post-gamma irradiation and shipping, and monthly until 180 d post-milling in feed. Amoxicillin concentrations in RO and tap water varied between 1.18 and 1.29 mg/ml, and 1.09 and 1.22 mg/ml, respectively. The concentration of amoxicillin declined immediately and remained between 0.43 and 0.50 mg/ml in acidified water. Clavulanic acid exhibited a slow time-dependent decrease in concentration to 0.05 mg/ml at day 7 in RO water, immediately declined and varied from 0.02 to 0.05 mg/ml in tap water, and was undetectable in acidified water. Trimethoprim and sulfamethoxazole concentrations were near expected in RO, tap, and acidified water. In food, amoxicillin, trimethoprim, and sulfamethoxazole concentrations were each reduced to approximately 60% of expected after pelleting, but remained stable thereafter for 180 d. The initial clavulanic acid concentration in feed was less than 10% of expected and was undetectable after 1 mo. Plasma drug concentrations were determined in C57BL/6NCrl mice at 4 h after commencement of the dark and light cycles following administration of antibiotic food for at least 72 h. Plasma amoxicillin and sulfamethoxazole concentrations were 3- and 10-fold greater, respectively, during the dark period. Plasma levels of clavulanic acid and trimethoprim were consistent at both time points. These results indicate that the antibiotic concentration can be influenced by compounding in feed and water, and differs in plasma during the light and dark phases of the photoperiod.
我们评估了两种抗生素组合，即阿莫西林 - 克拉维酸和甲氧苄啶 - 磺胺甲恶唑，在反渗透（RO）水（pH 6.0）、自来水（pH 6.7）和酸化水（pH 2.6）中混合7天的浓度，以及制粒前后、伽马射线辐照后和运输后，直至饲料制粒后180天每月的浓度。RO水和自来水中阿莫西林的浓度分别在1.18至1.29毫克/毫升和1.09至1.22毫克/毫升之间变化。阿莫西林在酸化水中的浓度立即下降，并保持在0.43至0.50毫克/毫升之间。克拉维酸在RO水中浓度呈现随时间缓慢下降，至第7天降至0.05毫克/毫升，在自来水中立即下降，浓度在0.02至0.05毫克/毫升之间变化，在酸化水中未检测到。甲氧苄啶和磺胺甲恶唑在RO水、自来水和酸化水中的浓度接近预期。在饲料中，制粒后阿莫西林、甲氧苄啶和磺胺甲恶唑的浓度均降至预期浓度的约60%，但此后180天保持稳定。饲料中初始克拉维酸浓度低于预期的10%，1个月后未检测到。在给予抗生素饲料至少72小时后，在C57BL/6NCrl小鼠明暗周期开始后4小时测定血浆药物浓度。在黑暗期，血浆中阿莫西林和磺胺甲恶唑的浓度分别高出3倍和10倍。克拉维酸和甲氧苄啶的血浆水平在两个时间点均保持一致。这些结果表明，抗生素浓度会受到饲料和水中混合的影响，并且在光周期的明暗阶段血浆中浓度有所不同。
