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Abstract

Objective—To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs.

Animals—6 healthy adult dogs.

Procedure—Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device.

Results—Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 ± 0.07 hours, 0.372 ± 0.053 L/kg, and 6.53 ± 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 ± 0.57 hours. Half-life after SC administration was 0.98 ± 0.21 and 1.31 ± 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%.

Conclusions and Clinical Relevance—Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 µg/mL. (Am J Vet Res 2002;63:1622–1628)

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in American Journal of Veterinary Research

Abstract

Objective—To compare plasma (total and unbound) and interstitial fluid (ISF) concentrations of doxycycline and meropenem in dogs following constant rate IV infusion of each drug.

Animals—6 adult Beagles.

Procedure—Dogs were given a loading dose of doxycycline and meropenem followed by a constant rate IV infusion of each drug to maintain an 8-hour steady state concentration. Interstitial fluid was collected with an ultrafiltration device. Plasma and ISF were analyzed by high performance liquid chromatography. Protein binding and lipophilicity were determined. Plasma data were analyzed by use of compartmental methods.

Results—Compared with meropenem, doxycycline had higher protein binding (11.87% [previously published value] vs 91.75 ± 0.63%) and lipophilicity (partition coefficients, 0.02 ± 0.01 vs 0.68 ± 0.05). A significant difference was found between ISF and plasma total doxycycline concentrations. No significant difference was found between ISF and plasma unbound doxycycline concentrations. Concentrations of meropenem in ISF and plasma (total and unbound) were similar. Plasma half-life, volume of distribution, and clearance were 4.56 ± 0.57 hours, 0.65 ± 0.82 L/kg, and 1.66 ± 2.21 mL/min/kg, respectively, for doxycycline and 0.73 ± 0.07 hours, 0.34 ± 0.06 L/kg, and 5.65 ± 2.76 mL/min/kg, respectively, for meropenem. The ISF half-life of doxycycline and meropenem was 4.94 ± 0.67 and 2.31 ± 0.36 hours, respectively.

Conclusions and Clinical Relevance—The extent of protein binding determines distribution of doxycycline and meropenem into ISF. As a result of high protein binding, ISF doxycycline concentrations are lower than plasma total doxycycline concentrations. Concentrations of meropenem in ISF can be predicted from plasma total meropenem concentrations. (Am J Vet Res 2003;64:1040–1046)

Full access
in American Journal of Veterinary Research