Pharmacokinetics of enrofloxacin after single intravenous, intramuscular and subcutaneous injections in lactating cows

Abstract

Five Ayrshire cows were given enrofloxacin (5 mg/kg body weight) intravenously (i.v.), intramuscularly (i.m.) and subcutaneously (s.c.). The antimicrobial activity was measured in milk and serum samples using the agar-diffusion technique. High-performance liquid chromatography (HPLC) assay was used to study the extent of metabolism of enrofloxacin to ciprofloxacin. Analysis of the serum concentration-time data was based on statistical moment theory. Mean t1/2 beta of antimicrobial activity in serum was 1.7, 5.9 and 5.6 h after i.v., i.m. and s.c. administration, respectively. Both i.m. and s.c. routes were associated with a marked flip-flop phenomenon. Based on HPLC analysis of serum samples, the half-lives of enrofloxacin and ciprofloxacin were approximately the same. A marked proportion of enrofloxacin was metabolized to ciprofloxacin. The enrofloxacin fraction bound in vitro to serum proteins was 36-45%. About 0.2% of the total enrofloxacin dose was found in milk during the first 24 h and the amount transferred did not depend on the route of administration. Based on the HPLC data, enrofloxacin concentration in milk was parallel to that in serum, while ciprofloxacin was concentrated in milk. After i.v. injection, the peak concentration of enrofloxacin in milk was reached between 0.7 and 1.3 h but occurred much later for ciprofloxacin (tmax 5-8 h). After i.m. and s.c. administration the concentration-time curves for both enrofloxacin and ciprofloxacin in milk were shallow and there were no obvious peaks.

Serum and milk concentrations of enrofloxacin in cows intramammarily treated with a new enrofloxacin-polymorph

“…This parameter is in agreement with MRT values found in this study (from 6.8 to 9.5 for enrofloxacin and from 8.8 to 17.7 for ciprofloxacin), which are slightly faster than previously reported ones (14,16). Intramuscular administration of a standard preparation of enrofloxacin at a dose of 5 mg/kg results in a MRT of 7.8 h (31).…”

“…As no previous reference to a dose through the mammary route is available in the literature, a relatively high intramammary dose was chosen in an attempt to comply with high concentrations of enrofloxacin at this target site. In agreement with absorption, elimination half life (T½β) ranged from 2.4 to 2.8 h, a shorter value than previously reported for the standard preparation of enrofloxacin (approximately 6 h) (14).…”

“…Sub-effective concentrations in milk and/or insufficient contact time with the affected mammary tissue are common causes for antibiotic failure (26). While parenteral enrofloxacin preparations are not usually recommended to treat bovine mastitis due to Staphylococcus aureus, high milk concentrations of enrofloxacin and its main metabolite (ciprofloxacin) are reached and maintained after parenteral administration (14). However, it must be considered that actual antibacterial activity can be partly impaired by the presence of milk and inflammatory secretions (10).…”

“…Furthermore, the added antibacterial contributions of enrofloxacin and ciprofloxacin should result in a considerably higher antibacterial activity than the sum of their independent antibacterial effects (18,26). This is particularly important, considering that only 2 to 3 µg/mL of enrofloxacin are found in milk after a standard dose of enrofloxacin, injected IM (13,14), and that cow's polymorphism can be a clinically relevant factor affecting the concentrations of enrofloxacin and ciprofloxacin in milk after parenteral administration of the drug (23).…”

Eficácia do dipropionato de imidocarb, da enrofloxacina e do cloridrato de oxitetraciclina no tratamento de bovinos naturalmente infectados por Anaplasma marginale

“…Em relação ao tratamento da anaplasmose bovina, alguns princípios ativos já apresentaram efeitos satisfatórios contra a infecção, como o cloridrato de oxitetraciclina (Pereira-Maia et al, 2010), o dipropionato de imidocarb (Melo e Carvalho Neta, 2009) e a enrofloxacina (Kaartinen et al, 1995). Apesar desses estudos sobre o tratamento e controle da anaplasmose, ainda existem dúvidas quanto ao tempo necessário para controlar a infecção e à duração desses efeitos contra o parasito.…”