Plasma disposition of amikacin and interactions with gastrointestinal microflora in Equidae following intravenous and oral administration

Abstract

Amikacin was detectable (> 0.02 micrograms/ml) in plasma for 12 h in horses and donkeys and for 8 h in ponies following intravenous (i.v.) administration at a dose rate of 6 mg/kg bodyweight. The elimination half-life (harmonic mean) of amikacin was 2.8, 1.6 and 1.9 h in horses, ponies and donkeys, respectively, and the mean body clearance was relatively slow (45.2, 82.4 and 58.0 ml/h.kg, respectively). A suitable dosage interval for the i.v. administration of amikacin sulphate to horses, ponies and donkeys, at a dose rate of 6 mg/kg, would be every 8 h in horses, and every 6 h in ponies and donkeys. Following i.v. administration there were no marked alterations in caecal liquor pH, the number of viable bacteria isolated, or the short chain fatty acid (SCFA) concentrations in caecal liquor and faeces. Amikacin was not detected (< 0.02 micrograms/ml) in plasma following administration by nasogastric tube to ponies with cannulated caecal fistulae; however, there were high concentrations of amikacin measured in caecal liquor (maximum 16.2-99.4 micrograms/ml). Despite the high drug concentrations in caecal liquor, there were only slight alterations in the number of viable bacteria isolated. However, there was a reduction in caecal liquor pH to < 6.6, but few changes in caecal liquor SCFA concentrations. Faecal SCFA concentrations, dry matter content and consistency did not alter markedly.

Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

“…(1994). The MRT for our study was significantly shorter than the 4 h previously reported by Horspool et al . (1994).…”

“…injection of amikacin (10 mg/kg bwt) in mature horses resulted in pharmacokinetic data partially similar to those found in previous studies performed in mature horses when 11 and 6.6 mg/kg bwt (Orsini et al . 1985) or 6 mg/kg bwt (Horspool et al . 1994) were administered i.v.…”

Pharmacological and pharmacokinetic differences between donkeys and horses

“…Amikacin Two similar studies with horses showed inconsistent values for elimination half-life (T 1 /2β), total body clearance (Cl B ) and apparent volume of distribution (area) (Vd AUC ) (Orsini et al 1985;Horspool et al 1994). When comparing these values with those for donkeys (Horspool et al 1994), both studies with horses showed important differences. A dose of 6 mg/kg was recommended either b.i.d.…”

“…(Orsini et al 1985) or t.i.d. (Horspool et al 1994) for horses and q.i.d. for donkeys (Horspool et al 1994).…”

“…Hence, it is reasonable to expect differences in the disposition of drugs between these species, which may alter dosing intervals (Kinabo and Bogan 1989;Horspool and McKellar 1990;Horspool et al 1994;Mealey et al 1997). Table 1a,b summarises the values available for pharmacokinetic variables for drugs in donkeys and the corresponding values for horses.…”