Abstract
A calf tissue cage model was used to study the pharmacokinetics (PK) and pharmacodynamics (PD) of oxytetracycline in serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids. After intramuscular administration, the PK was characterized by a long mean residence time of 28.3hr. Based on minimum inhibitory concentrations (MICs) for six isolates each of Mannheimia haemolytica and Pasteurella multocida, measured in serum, integration of in vivo PK and in vitro PD data established area under serum concentration-time curve (AUC0-∞ )/MIC ratios of 30.0 and 24.3hr for M.haemolytica and P.multocida, respectively. Corresponding AUC0-∞ /MIC ratios based on MICs in broth were 656 and 745hr, respectively. PK-PD modelling of in vitro bacterial time-kill curves for oxytetracycline in serum established mean AUC0-24hr /MIC ratios for 3log10 decrease in bacterial count of 27.5hr (M.haemolytica) and 60.9hr (P.multocida). Monte Carlo simulations predicted target attainment rate (TAR) dosages. Based on the potency of oxytetracycline in serum, the predicted 50% TAR single doses required to achieve a bacteriostatic action covering 48-hr periods were 197mg/kg (M.haemolytica) and 314mg/kg (P.multocida), respectively, against susceptible populations. Dosages based on the potency of oxytetracycline in broth were 25- and 27-fold lower (7.8 and 11.5mg/kg) for M.haemolytica and P.multocida, respectively.
Highlights
The spectrum of activity of oxytetracycline includes two major bacterial species causing bovine pneumonia, Mannheimia haemolytica and Pasteurella multocida (Nouws et al, 1985; Nouws et al, 1985; Nouws et al, 1990)
Oxytetracycline remains in extensive use for the treatment of calf pneumonia as it possesses the advantage of availability in both low
Dosages for oxytetracycline were set many years ago and it may be appropriate to reevaluate them in light of currently accepted PK/pharmacodynamic (PD) concepts
Summary
The spectrum of activity of oxytetracycline includes two major bacterial species causing bovine pneumonia, Mannheimia haemolytica and Pasteurella multocida (Nouws et al, 1985; Nouws et al, 1985; Nouws et al, 1990). 10%w/v) and high (20-30%w/v) strength injectable products The latter provide high dose (20-30mg/kg) long acting formulations; single dose therapy may be clinically effective when these formulations are administered intramuscularly. These depot formulations provide sustained absorption from the intramuscular injection site, leading to flip-flop pharmacokinetics (PK) (Nouws & Vree, 1983; Toutain & Raynaud, 1983; Nouws et al., 1990). Dosages for oxytetracycline were set many years ago and it may be appropriate to reevaluate them in light of currently accepted PK/pharmacodynamic (PD) concepts.
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