Objective-To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age. Animals-24 female pigs. Procedure-At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetium Tc 99m pentetate was calculated. Results-Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance ( r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight. Conclusions-Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple blood samples in pigs from 3 to 24 weeks of age.

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.

Objective-To evaluate effects of age and body size of dogs on intestinal permeability (unmediated diffusion) as measured by the ratio of urinary lactulose to L-rhamnose (L:R) and absorption (carrier-mediated transport) as measured by the ratio of urinary D-xylose to 3-O-methyl-D-glucose (X:MG) and to determine whether these variables correlated with fecal quality. Animals-6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. Procedure-A solution that contained lactulose and rhamnose or xylose and 3-O-methyl-D-glucose was administered orally to dogs that were 12, 22, 36, and 60 weeks old. Urine was collected 6 hours later, and urinary L:R and X:MG were calculated. Fecal moisture and scoring were recorded during the same periods. Results-Age and breed did not affect intestinal absorption, and we did not detect a relationship between X:MG and fecal variables. In contrast, we detected significant effects of age and body size on intestinal permeability. Puppies (12 weeks old) and large dogs had higher intestinal permeability than adult (60 weeks old) and small dogs. The increased intestinal permeability in large dogs was associated with lower fecal quality as indicated by the significant positive correlations between L:R and fecal moisture (r, 0.61) and L:R and fecal scores (r, 0.86) in adult dogs. Conclusion and Clinical Relevance-These results indicate that age and body size should be considered when assessing intestinal permeability by use of the L:R urinary excretion test in dogs. High intestinal permeability could be a possible cause of poor fecal quality in large dogs.