Pharmacokinetics and lung tissue concentrations of tulathromycin in swine.
The absolute bioavailability and lung tissue distribution of the triamilide antimicrobial, tulathromycin, were investigated in swine. Fifty-six pigs received 2.5 mg/kg of tulathromycin 10% formulation by either intramuscular (i.m.) or intravenous (i.v.) route in two studies: study A (10 pigs, i.m. and 10 pigs, i.v.) and study B (36 pigs, i.m.). After i.m. administration the mean maximum plasma concentration (C(max)) was 616 ng/mL, which was reached by 0.25 h postinjection (t(max)). The mean apparent elimination half-life (t(1/2)) in plasma was 75.6 h. After i.v. injection plasma clearance (Cl) was 181 mL/kg.h, the volume of distribution at steady-state (V(ss)) was 13.2 L/kg and the elimination t(1/2) was 67.5 h. The systemic bioavailability following i.m. administration was >87% and the ratio of lung drug concentration for i.m. vs. i.v. injection was > or =0.96. Following i.m. administration, a mean tulathromycin concentration of 2840 ng/g was detected in lung tissue at 12 h postdosing. The mean lung C(max) of 3470 ng/g was reached by 24 h postdose (t(max)). Mean lung drug concentrations after 6 and 10 days were 1700 and 1240 ng/g, respectively. The AUC(inf) was 61.4 times greater for the lung than for plasma. The apparent elimination t(1/2) for tulathromycin in the lung was 142 h (6 days). Following i.m. administration to pigs at 2.5 mg/kg body weight, tulathromycin was rapidly absorbed and highly bioavailable. The high distribution to lung and slow elimination following a single dose of tulathromycin, are desirable pharmacokinetic attributes for an antimicrobial drug indicated for the treatment of respiratory disease in swine.
Pfizer Animal Health, Veterinary Medicine Research and Development, Pfizer Ltd., Sandwich, Kent CT13 9NJ, UK. hbenchaoui@pfizer.com
H A
HA
Benchaoui
M
M
Nowakowski
J
J
Sherington
T G
TG
Rowan
S J
SJ
Sunderland
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004187:Disaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008168:Lung / Q000378:metabolism*; D008297:Male; D013552:Swine / Q000378:metabolism*; D018942:Macrolides
D000890:Anti-Infective Agents; D004187:Disaccharides; D006571:Heterocyclic Compounds; C485204:tulathromycin; D018942:Macrolides