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)
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
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)