Comparison of plasma and interstitial fluid concentrations of doxycycline and meropenem following constant rate intravenous infusion in dogs

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. ANIMAL: 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.     

Evaluation of iohexol clearance used to estimate glomerular filtration rate in clinically normal foals

OBJECTIVE: To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. ANIMALS: 10 healthy foals. PROCEDURE: Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. RESULTS: Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. CONCLUSIONS AND CLINICAL RELEVANCE: Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after i.v. injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.     

Aggressive behavior is reduced in bulls actively immunized against gonadotropin-releasing hormone

The purpose of this research was to compare the frequency of aggressive behavior's in beef bulls actively immunized against gonadotropin-releasing hormone relative to contemporary nonimmunized control bulls and surgically castrated steers. Eight males were assigned to each ofthese treatments in each of 4 yr. Immunized males were treated with a GnRH-keyhole-limpet hemocyanin (KLH) conjugate at approximately 4 mo of age. A secondary (booster) immunization was administered at 12 mo. Steers were castrated at 4 mo of age. Animals in each treatment in each year were housed as a single group prior to testing. At approximately 16 mo of age, each group of eight animals was placed in a 10- x 16-m enclosure for 20 min on five occasions at 2 to 3 d intervals. An observer recorded butts initiated by each animal as well as participation in bouts of sparring. Relative to control bulls, immunocastration reduced the frequency of butts initiated (P < 0.05) and participation in sparring bouts (P < 0.05) to levels typically observed in steers (P > 0.05). These observations indicate that active immunization against GnRH reduces the incidence of aggressive behavior in male beef cattle and are consistent with our postulate that immunoneutralization of GnRH is an effective alternative to surgical castration in the management of beef cattle.     

Isoflurane to prolong medetomidine/ ketamine anaesthesia in six adult female chimpanzees (Pan troglodytes)

Six adult female chimpanzees (Pan troglodytes) were anaesthetised for the placement of intrauterine contraceptive devices, microchips for identification, routine blood sampling, and physical measurements. Anaesthesia was induced with medetomidine in combination with ketamine administered by intramuscular injection with a projectile syringe. Induction was smooth and rapid, but five of the animals were insufficiently relaxed for orotracheal intubation. The plane of anaesthesia was deepened by administering isoflurane delivered in oxygen and nitrous oxide, and general anaesthesia was maintained for up to 74 minutes. The action of medetomidine was reversed at the end of each procedure with atipamezole, and the animals recovered smoothly and uneventfully.     

Influence of vestibulovaginal stenosis,pelvic bladder,and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs: 38 cases (1990-1999)

OBJECTIVE: To determine influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs. DESIGN: Retrospective study. ANIMALS: 38 spayed female dogs. PROCEDURE: Medical records and client follow-up were reviewed for dogs evaluated via excretory urography because of clinical signs of lower urinary tract disease. Clinical signs, results of radiography, and response to surgical or medical treatment were analyzed. RESULTS: Clinical signs included urinary tract infection (n = 24), urinary incontinence (20), vaginitis (11), pollakiuria or stranguria (10), and perivulvar dermatitis (4). Vaginocystourethrographic findings included vestibulovaginal stenosis (n = 28), pelvic bladder (17), and ureteritis or pyelonephritis (4). Ten dogs had a vestibulovaginal ratio of < 0.20 (severe stenosis), 9 dogs had a ratio of 0.20 to 0.25 (moderate stenosis), 9 dogs had a ratio of 0.26 to 0.35 (mild stenosis), and 10 dogs had a ratio of > 0.35 (anatomically normal). Lower urinary tract infection, incontinence, and pelvic bladder were not associated with response to treatment for recessed vulva. Vestibulovaginal stenosis with a ratio < 0.20 was significantly associated negatively with response to treatment. Dogs without severe vestibulovaginal stenosis that received vulvoplasty for a recessed vulva responded well to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Vestibulovaginal stenosis is likely an important factor in dogs with vestibulovaginal ratio < 0.20. Vaginectomy or resection and anastomosis should be considered in dogs with severe vestibulovaginal stenosis and signs of lower urinary tract disease.     

Identification of a new source of Campylobacter contamination in poultry: transmission from breeder hens to broiler chickens

Campylobacter jejuni, a foodborne pathogen closely associated with market poultry, is considered to be the most frequent agent of human gastroenteritis in the United States. The pathways involved in the contamination of poultry flocks, vertical transmission and/or horizontal transmission, are unclear. In this study, Campylobacter isolates from two independent commercial broiler breeder flocks, as well as from their respective progeny, were characterized and compared by PstI ribotype analysis and by DNA sequence analysis of the short variable region (SVR) of the flaA gene (flaA SVR). Campylobacter isolates originating from one set of breeder hens and the feces from their respective progeny demonstrated identical ribotype patterns as well as identical flaA SVR DNA sequences, thereby suggesting that these isolates were clonal in origin. Ribotype analysis of Campylobacter isolates from the second set of breeder hens and processed carcasses from their offspring resulted in two patterns. Sequence analysis placed these isolates into two closely related groups and one distant group, similar to the ribotype analysis. These results demonstrate that Campylobacter isolates from commercial broiler breeder flocks and from the respective broiler progeny may be of clonal origin and that breeder hens can serve as a source for Campylobacter contamination in poultry flocks.