Potassium penicillin and gentamicin pharmacokinetics in healthy conscious and anesthetized horses

Abstract

To determine the effects of general anesthesia on the safety and efficacy of co-administered potassium penicillin G (PEN) and gentamicin (GENT) in horses. Study design: Nonrandomized crossover.Animals: Six adult, Thoroughbred horses.Methods: Horses were administered PEN (22 000 IU/kg IV) and GENT (6.6 mg/kg IV). Plasma samples were collected over a 6 h period and synovial fluid was collected at 30 min and 6 h respectively. Drug administration and sample collection protocols were repeated after at least a 48 hour washout period and induction of anesthesia using xylazine/ketamine and maintenance with isoflurane gas. Drug concentrations were determined using ultrapressure liquid chromatography with mass spectrometry. A 2-compartment model was used to determine pharmacokinetics and differences were determined between conscious and anesthetized horses using paired t-tests (significance P < .05).Results: Potassium penicillin g and GENT had higher minimum plasma concentrations (PEN 0.44 vs. 0.11 μg/mL, P = .002; GENT 3.0 vs. 1.9 μg/mL, P = .009), longer half lives (PEN 71 vs. 59 min, P = .018; GENT 149 vs. 109 min, P = .038), and slower clearances (PEN 3.41 vs. 5.1 mL/kg/min, P = .005; GENT 1.18 vs. 1.48 mL/kg/min, P = .028) in anesthetized horses vs. conscious horses. The PEN concentrations remained above the breakpoint minimum inhibitory concentration (MIC, 0.5 μg/mL) for 332 min in anesthetized vs. 199 min in conscious horses. The GENT concentrations reached 10 times higher than the breakpoint MIC (2 μg/mL) in all horses and were maintained for 58 vs. 59 min in anesthetized and conscious states, respectively. Synovial fluid concentrations were higher in conscious horses vs. anesthetized horses at 30 min for PEN (7.0 vs. 0.93 μg/mL, P < .001) and 30 (5.3 μg/mL vs. 0.79 μg/mL, P < .001) and 360 min (3.4 vs. 1.82 μg/mL, P < .003) for GENT. Conclusion: General anesthesia resulted in lower intrasynovial concentrations and delayed clearance of PEN/GENT in horses.

Pharmacokinetic–pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses

“…Raw data collected in four countries (France, Sweden, the USA, and Japan) were considered. Some of the datasets USA1 (Younkin et al, 2019), USA2 (Wilson et al, 2022), and Sweden (Olsén et al, 2013(Olsén et al, , 2018 have previously been published, but the French data were specifically generated for this project. The Japanese data have not been published.…”

“…In USA1, seven horses received two IV administrations of potassium BP, followed by a single dose of procaine BP (Younkin et al, 2019). In USA2, six horses received a single IV administration of potassium BP in association with gentamicin (Wilson et al, 2022). In Sweden, four horses received a single IV dose of sodium BP (Olsén et al, 2018) and eight other horses were enrolled in a 2 × 2 crossover design aiming to compare a series of four IM administrations of procaine BP and a series of seven IM administrations of sodium BP at 12 h intervals (Olsén et al, 2013).…”

Pharmacokinetics of Single Intramuscular Administration of Ceftiofur Crystalline Free Acid in American Alligators (Alligator Mississippiensis)

“…Noncompartmental analysis was also used to estimate time based above target threshold concentrations for ceftiofur equivalents in American alligators (2 and 4 µg/ml) as previously described ( t >2 and t >4 ). 42…”

Surgical antimicrobial prophylaxis: Current standards of care

“…Penicillin G's half‐life is 48–53 min (Durr, 1976; Love et al, 1983) and, therefore, recommendations have been made for dosing every 2 h during surgery. Recently, however, plasma potassium penicillin concentrations were shown to remain above the MIC (0.5 μg/mL) for 332 min in anaesthetised compared with 199 min in conscious healthy horses, suggesting that clearance is delayed in anaesthetised horses and that re‐dosing for most procedures before 4–5 h is unnecessary (Wilson et al, 2023). Importantly, in the latter study, synovial concentrations of potassium penicillin and gentamicin were lower in anaesthetised than conscious horses indicating that local antimicrobial administration may be more effective.…”