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Summary

Enrofloxacin was administered orally to 6 healthy dogs at dosages of approximately 2.75, 5.5, and 11 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosage regimens. Serum and tissue cage fluid (tcf) concentrations of enrofloxacin were measured after the first and seventh treatments. The mean peak serum concentration occurred between 1 and 2.5 hours after dosing. Peak serum concentrations increased with increases in dosage. For each dosage regimen, there was an accumulation of enrofloxacin between the first and seventh treatment, as demonstrated by a significant (P = 0.001) increase in peak serum concentrations. The serum elimination half-life increased from 3.39 hours for the 2.75 mg/kg dosage to 4.94 hours for the 11 mg/kg dosage. Enrofloxacin accumulated slowly into tcf, with peak concentrations being approximately 58% of those of serum. The time of peak tcf concentrations occurred between 3.8 hours and 5.9 hours after drug administration, depending on the dosage and whether it was after single or multiple administrations. Compared with serum concentrations (area under the curve tcf /area under the curveserum), the percentage of enrofloxacin penetration into tcf was 85% at a dosage of 2.75 mg/kg, 83% at a dosage of 5.5 mg/kg, and 88% at a dosage of 11 mg/kg. All 3 dosage regimens of enrofloxacin induced continuous serum and tcf concentrations greater than the minimal concentration required to inhibit 90% (mic 90) of the aerobic and facultative anaerobic clinical isolates tested, except Pseudomonas aeruginosa. Only the 11 mg/kg dosage regimen provided continuous serum and tcf concentrations that exceeded the mic 90 for P aeruginosa isolates; whereas none of the dosages induced serum or tcf concentrations greater than the mic 90 of the obligate anaerobic bacteria tested.

Free access
in American Journal of Veterinary Research

SUMMARY

Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following IV administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin against an equine clinical isolate of Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted in maximal serum concentrations (77.93 ± 19.90 μg/ml, mean ± sem) and area under the concentration-vs-time curves (83.79 ± 14.97 μg.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 ± 0.50 μg/ml and 6.03 ± 0.66 μg.h/ml, respectively). Nephrotoxicosis was not induced with either dosage regimen, and postantibiotic effects were prolonged with a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.

Free access
in American Journal of Veterinary Research

Summary

Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (tcf) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean ± sem; 5.68 ± 0.54 μg/ml) and least in the tcf after a single dose of 11 mg/kg (0.43 ± 0.54 μg/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for tcf (6.41 ± 0.52 hour) than for serum (1.53 ± 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0→12). The AUC0→12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 ± 1.90 μg·h/ml) and least in the tcf after a single dose of 11 mg/kg (3.87 ± 1.90 μg·h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for tcf (14.59 ± 1.91 hours) than for serum (5.14 ± 1.91 hours). The percentage of tcf penetration (AUCTCF/AUCserum ) was greater after multiple doses (95.76 ± 6.79%) than after a single dose (55.55 ± 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and tcf concentrations > 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.

Free access
in American Journal of Veterinary Research