Poźniak Błażej, Tikhomirov Marta, Bobrek Kamila, Jajor Paweł, Świtała Marcin
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, ul. Norwida 31, 50-375 Wrocław, Poland.
Department of Epizootiology and Clinic of Birds and Exotic Animals, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, pl. Grunwaldzki 45, 50-366 Wrocław, Poland.
Antibiotics (Basel). 2021 Aug 31;10(9):1057. doi: 10.3390/antibiotics10091057.
Turkeys' body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistance. The study aimed to investigate whether a non-linear dosage based on a published allometric model for tylosin clearance, may optimize the internal exposure in growing turkeys. The single dose PK study was performed on turkeys aged 6, 9.5, 13 and 17 weeks (BW from 1.75 kg to 15.75 kg). Tylosin was administered intravenously (i.v.) or orally (p.o.) according to following protocols: Dose = 31.6 × BW or Dose = 158 × BW, respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUC) after i.v. administration was 8.90 ± 1.01; 7.51 ± 1.11; 6.54 ± 1.20 and 8.01 ± 1.75 mg × h/L in 6-; 9.5-; 13- and 17-week-old turkeys, respectively. After p.o. administration AUC was 4.80 ± 2.92; 4.60 ± 2.45; 3.00 ± 1.49 and 3.24 ± 2.00 mg × h/L in respective age groups indicating high variability. For i.v. administration, the non-linear dosage allowed to minimize the age-dependent variability in AUC. However, due to low oral bioavailability (8-12%) and resulting interindividual variability, the proposed approach may not improve tylosin efficacy in turkeys under farm conditions.
火鸡的体重(BW)在短短2.5个月内增长10倍,根据异速生长原理,这会导致药物药代动力学(PK)发生变化。因此,相同剂量可能会导致疗效出现年龄依赖性差异,尤其是导致治疗失败和/或产生耐药性。本研究旨在调查基于已发表的泰乐菌素清除率异速生长模型的非线性剂量是否可以优化生长中火鸡的体内暴露量。对6、9.5、13和17周龄(体重从1.75千克至15.75千克)的火鸡进行了单剂量PK研究。根据以下方案静脉注射(i.v.)或口服(p.o.)泰乐菌素:剂量分别为31.6×体重或158×体重。使用高效液相色谱法测量血浆泰乐菌素,并进行非房室PK分析。静脉注射给药后的曲线下面积(AUC)在6周龄、9.5周龄、13周龄和17周龄的火鸡中分别为8.90±1.01;7.51±1.11;6.54±1.20和8.01±1.75毫克·小时/升。口服给药后,各年龄组的AUC分别为4.80±2.92;4.60±2.45;3.00±1.49和3.24±2.00毫克·小时/升,表明变异性很大。对于静脉注射给药,非线性剂量能够使AUC中的年龄依赖性差异最小化。然而,由于口服生物利用度低(8 - 12%)以及由此产生的个体间变异性,所提出的方法可能无法提高农场条件下火鸡的泰乐菌素疗效。