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)