Pharmacokinetics and estimated bioavailability of amoxicillin in mares after intravenous, intramuscular, and oral administration

The pharmacokinetics and estimated bioavailability of amoxicillin were determined after IV, intragastric, and IM administration to healthy mares. After IV administration of sodium amoxicillin (10 mg/kg of body weight), the disposition of the drug was best described by a 2-compartment open model. A rapid distribution phase was followed by a rapid elimination phase, with a mean +/- SD half-life of 39.4 +/- 3.57 minutes. The mean volume of distribution was 325 +/- 68.2 ml/kg, and the mean body clearance was 5.68 +/- 0.80 ml/min.kg. It was concluded that frequent IV administration of sodium amoxicillin would be required to maintain therapeutic plasma concentrations of amoxicillin, and thus, the use of this dosage form should be limited to the initiation of treatment or to intensive care situations. After intragastric administration of amoxicillin trihydrate (20 mg/kg), 5% cherry-flavored suspension, the drug was rapidly, but incompletely, absorbed and rapidly eliminated (mean half-life of the decline phase of the plasma amoxicillin concentration-time curve, 51 minutes). The mean estimated bioavailability (fractional absorption) of the administered dose was 10.4%, and the mean peak plasma amoxicillin concentration was 2.73 microgram/ml at 1.5 hours after dosing. In one horse with clinical signs of abdominal discomfort and diarrhea, the absorption of amoxicillin from the gastrointestinal tract was delayed and the fraction absorbed was increased. It was concluded that this oral dosage form could be recommended only for the treatment of infections caused by bacteria that are highly susceptible to amoxicillin, that frequent dosing would be necessary, and that absorption may be inconsistent in horses with gastrointestinal disease. In 2 subsequent phases, amoxicillin trihydrate (10 mg/kg) was administered IM as either a 10% (100 mg/ml) or a 25% (250 mg/ml) aqueous suspension. For both formulations, plasma amoxicillin concentration peaked 45 minutes after dosing (2.08 microgram/ml for the 10% suspension and 0.98 microgram/ml for the 25% suspension). Thereafter, mean amoxicillin concentrations > 0.5 microgram/ml persisted for 24 hours, and the values achieved with the 10% suspension were approximately twice as high as those achieved with the 25% suspension throughout the sample collection period. It was estimated that absorption was complete (100%) within 24 hours after IM administration of the dose as 10% aqueous suspension, but was incomplete by 24 hours after administering the same dose as a 25% suspension. This suggests that a large portion of the latter dose remained as a precipitate at the injection site. It was concluded that amoxicillin trihydrate should be administered IM to horses as a 10%, rather than a 25%, suspension. A dosage of 10 mg/kg administered at 12-hour intervals should maintain plasma concentrations > 1 microgram/ml and should be effective in treating infections caused by bacteria that are inhibited by low concentrations of amoxicillin. This dosage regimen does not constitute broad-spectrum treatment and may be limited by the relatively large injection volume and the discomfort associated with administration.