Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute, SVA, 751 89, Uppsala, Sweden.
Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Husbandry, Swedish University of Agricultural Sciences, Box 7028, 750 07, Uppsala, Sweden.
Acta Vet Scand. 2020 Sep 17;62(1):55. doi: 10.1186/s13028-020-00552-0.
Penicillin is important for treatment of pigs, but data on its absorption and disposition in pigs are sparse. This is reflected by the variation in recommended dosages in the literature. Inadequate dosage may lead to treatment failure and selection of resistant bacteria. To optimize treatment regimens, plasma exposure to benzylpenicillin for two sustained release formulations of procaine benzylpenicillin for intramuscular administration was studied in growing pigs by means of tandem mass spectrometry (UPLC-MS/MS). One formulation was an aqueous suspension, Ethacilin® vet (ETH), and the other an oily suspension, Ultrapen vet (UPA). Benzylpenicillin exposure after intravenous administration of potassium benzylpenicillin was also explored. Exposure profiles were first studied after single administrations of the approved dosages in healthy pigs and then after repeated administration of different dosages in pigs inoculated intranasally with an Actinobacillus pleuropneumoniae serotype 2 strain.
After intravenous administration of benzylpenicillin (n = 6), maximum plasma concentration (C), 1860-9318 µg/L, was observed after 15 min. At four h, plasma concentrations decreased to 15-76 µg/L. After intramuscular administration of ETH (n = 6) C, 1000-4270 µg/L, was observed within one h (t) in 5 pigs but at four h in one pig. C for UPA (n = 6), 910-3220 µg/L, was observed within one h in three pigs, but at four or 24 h in three pigs. For both ETH and UPA, the terminal phase was characterized by slow decline compared with intravenous administration. Repeated administration of different dosages of ETH and UPA in pigs inoculated with A. pleuropneumoniae (n = 54) showed that the approved dose for UPA (30 mg/kg, qd) but not for ETH (20 mg/kg, qd) gave adequate plasma exposure for bacteria with a penicillin MIC of 500 µg/L. However, more frequent dosing of ETH (bid) or increased dosage gave an adequate exposure.
The approved dosage of ETH provided insufficient plasma exposure for adequate therapy of infections caused by A. pleuropneumoniae or other bacteria with a penicillin MIC of 500 µg/L. More frequent ETH dosing (bid) or an increased dosage would improve exposure. The approved dosage of UPA however provided adequate exposure.
青霉素对猪的治疗很重要，但有关其在猪体内吸收和分布的数据却很少。这反映在文献中推荐剂量的差异上。剂量不足可能导致治疗失败和耐药菌的选择。为了优化治疗方案，通过串联质谱法（UPLC-MS/MS）研究了两种普鲁卡因青霉素长效释放制剂——水混悬剂 Ethacilin® vet（ETH）和油混悬剂 Ultrapen vet（UPA）——用于肌肉注射时，猪体内的苄青霉素血浆暴露情况。还研究了静脉注射青霉素钾后苄青霉素的暴露情况。首先在健康猪单次给予批准剂量后研究了暴露曲线，然后在接种胸膜肺炎放线杆菌 2 型菌株的猪中重复给予不同剂量后进行了研究。
静脉注射苄青霉素（n=6）后，15 分钟时观察到最大血浆浓度（C）为 1860-9318μg/L。4 小时时，血浆浓度降至 15-76μg/L。肌肉注射 ETH（n=6）后，5 只猪在 1 小时（t）内观察到 C，为 1000-4270μg/L，但 1 只猪在 4 小时时观察到 C。肌肉注射 UPA（n=6）后，3 只猪在 1 小时内观察到 C，为 910-3220μg/L，但 3 只猪在 4 小时或 24 小时时观察到 C。与静脉注射相比，ETH 和 UPA 的终末相都表现为缓慢下降。接种胸膜肺炎放线杆菌的猪重复给予不同剂量的 ETH 和 UPA（n=54）显示，批准剂量的 UPA（30mg/kg，qd）而非 ETH（20mg/kg，qd）可使青霉素 MIC 为 500μg/L 的细菌获得足够的血浆暴露。然而，更频繁的 ETH 给药（bid）或增加剂量可获得足够的暴露。然而，批准剂量的 UPA 可提供足够的暴露。
批准的 ETH 剂量不能为青霉素 MIC 为 500μg/L 的胸膜肺炎放线杆菌或其他细菌引起的感染提供足够的血浆暴露，以进行充分治疗。更频繁的 ETH 给药（bid）或增加剂量可改善暴露。然而，批准剂量的 UPA 可提供足够的暴露。
