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Effect of age on the pharmacokinetics and distribution of tulathromycin in interstitial and pulmonary epithelial lining fluid in healthy calves

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  • 1 Food Animal Residue and Avoidance Databank, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 2 Food Animal Residue and Avoidance Databank, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 3 Food Animal Residue and Avoidance Databank, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 4 Office of New Animal Drug Evaluation, Center for Veterinary Medicine, 7500 Standish Pl, Metro Park North II, Room 390, Rockville, MD 20855.
  • | 5 Food Animal Residue and Avoidance Databank, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 6 Food Animal Residue and Avoidance Databank, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

OBJECTIVE To compare the plasma pharmacokinetics of tulathromycin between 3-week-old (preweaned) and 6-month-old (weaned) calves and to characterize the distribution of tulathromcyin into pulmonary epithelial lining fluid (PELF) and interstitial fluid (ISF) of preweaned and weaned calves following SC administration of a single dose (2.5 mg/kg).

ANIMALS 8 healthy 3-week-old and 8 healthy 6-month-old Holstein steers.

PROCEDURES A jugular catheter and SC ultrafiltration probe were aseptically placed in the neck of each calf before tulathromycin administration. Blood, ISF, and bronchoalveolar lavage fluid samples were collected at predetermined times before and after tulathromycin administration for quantification of drug concentration. A urea dilution method was used to estimate tulathromycin concentration in PELF from that in bronchoalveolar lavage fluid. Tulathromycin–plasma protein binding was determined by in vitro methods. Plasma pharmacokinetics were determined by a 2-compartment model. Pharmacokinetic parameters and drug concentrations were compared between preweaned and weaned calves.

RESULTS Clearance and volume of distribution per fraction of tulathromycin absorbed were significantly greater for weaned calves than preweaned calves. Tulathromycin–plasma protein binding was significantly greater for weaned calves than preweaned calves. Maximum PELF tulathromycin concentration was significantly greater than the maximum plasma and maximum ISF tulathromycin concentrations in both groups.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age affected multiple pharmacokinetic parameters of tulathromycin, likely owing to physiologic changes as calves mature from preruminants to ruminants. Knowledge of those changes may be useful in the development of studies to evaluate potential dose adjustments during treatment of calves with respiratory tract disease.

Abstract

OBJECTIVE To compare the plasma pharmacokinetics of tulathromycin between 3-week-old (preweaned) and 6-month-old (weaned) calves and to characterize the distribution of tulathromcyin into pulmonary epithelial lining fluid (PELF) and interstitial fluid (ISF) of preweaned and weaned calves following SC administration of a single dose (2.5 mg/kg).

ANIMALS 8 healthy 3-week-old and 8 healthy 6-month-old Holstein steers.

PROCEDURES A jugular catheter and SC ultrafiltration probe were aseptically placed in the neck of each calf before tulathromycin administration. Blood, ISF, and bronchoalveolar lavage fluid samples were collected at predetermined times before and after tulathromycin administration for quantification of drug concentration. A urea dilution method was used to estimate tulathromycin concentration in PELF from that in bronchoalveolar lavage fluid. Tulathromycin–plasma protein binding was determined by in vitro methods. Plasma pharmacokinetics were determined by a 2-compartment model. Pharmacokinetic parameters and drug concentrations were compared between preweaned and weaned calves.

RESULTS Clearance and volume of distribution per fraction of tulathromycin absorbed were significantly greater for weaned calves than preweaned calves. Tulathromycin–plasma protein binding was significantly greater for weaned calves than preweaned calves. Maximum PELF tulathromycin concentration was significantly greater than the maximum plasma and maximum ISF tulathromycin concentrations in both groups.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age affected multiple pharmacokinetic parameters of tulathromycin, likely owing to physiologic changes as calves mature from preruminants to ruminants. Knowledge of those changes may be useful in the development of studies to evaluate potential dose adjustments during treatment of calves with respiratory tract disease.

Contributor Notes

Address correspondence to Dr. Baynes (Ronald_Baynes@ncsu.edu).