Tilmicosin antibacterial activity and pharmacokinetics in cows

Abstract

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 microgram/mL and 149 of 164 (90.8%) other gram-positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 micrograms/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 microgram/mL when the test was conducted using Mueller-Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.-administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half-life (t1/2 beta) values for 3 cows were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half-life (t1/2el) was 4.18 +/- 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 microgram/mL were found in the secretion for 8-9 days after dosing. Systemic side-effects were not observed after s.c. drug administration.

Pharmacokinetics of Antimicrobials in Food Producing Animals

“…It has large volume of distribution (>2 L/ kg), with accumulation and persistence in tissues like lung. The drug administrated to cow (10 mg/kg, SC) resulted in milk concentration > 0.8 μg/ml for eight to nine days (Ziv et al,1995) …”

Pharmacokinetics, tissue residues of tilmicosin phosphate (tilmicor-al®) and its in vitro and in vivo evaluation for the control of Mycoplas-ma gallisepticum infection in broiler chickens

“…Tilmicosin is used for treatment and control of respiratory diseases caused by Mycoplasma gallisepticum, Mycoplasma synoviae, Pasteurella multocida and Ornithobacterium rhinotracheale in broiler chickens (Jordan & Christodoulopoulos et al 2002). The pharmacokinetics after parenteral administration of tilmicosin has been investigated in cow (Ziv et al 1995, Modric et al 1998, goat (Ramadan 1997), sheep (Modric et al 1998), and elk (Clark et al 2004). However, few studies are available on the pharmacokinetics of tilmicosin after oral administration to animals including fowl and swine (Keles et al 2001, Shen et al 2005.…”

Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil nanoparticle suspensions of different particle sizes

“…2 Thus, tilmicosin can be used for the treatment of bovine mastitis; however, tilmicosin can also cause acute cardiac toxicity. 2 Cattle can tolerate doses as high as 50 mg/kg if the drug is administered subcutaneously, but they have toxic reactions consistent with cardiovascular damage when injected intravenously, even at doses as low as 5 mg/kg. 4 Pigs also exhibit a toxic reaction to tilmicosin (increased respiration, emesis, and convulsions) at 10 mg/kg when administered intramuscularly.…”

“…2,3 Following intravenous or subcutaneous administration, tilmicosin rapidly passes from the blood into milk and is eliminated slowly from the milk. 2 Thus, tilmicosin can be used for the treatment of bovine mastitis; however, tilmicosin can also cause acute cardiac toxicity.…”

“…2,3 Following intravenous or subcutaneous administration, tilmicosin rapidly passes from the blood into milk and is eliminated slowly from the milk. 2 Thus, tilmicosin can be used for the treatment of bovine mastitis; however, tilmicosin can also cause acute cardiac toxicity. 2 Cattle can tolerate doses as high as 50 mg/kg if the drug is administered subcutaneously, but they have toxic reactions consistent with cardiovascular damage when injected intravenously, even at doses as low as 5 mg/kg.…”