Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys

Abstract

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^0.58 or Dose = 158 × BW^0.58, respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUC_last) 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_last 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.

Keywords: allometric scaling; dose optimization; internal exposure; pharmacokinetics; poultry; turkeys; tylosin.

Figure 1

Plasma tylosin A concentrations after single intravenous (upper panel) and oral dose (lower panel) of tylosin tartrate calculated according to the protocols: Dose = 31.6 × BW^0.58 or Dose = 158 × BW^0.58 for the intravenous and oral administration, respectively.

Figure 2

Plasma tylosin D concentrations after single intravenous dose of tylosin tartrate calculated according to the protocol: Dose = 31.6 × BW^0.58.