Objective—To determine pharmacokinetics of buprenorphine in dogs after IV administration.
Animals—6 healthy adult dogs.
Procedures—6 dogs received buprenorphine at 0.015 mg/kg, IV. Blood samples were collected at time 0 prior to drug administration and at 2, 5, 10, 15, 20, 30, 40, 60, 90, 120, 180, 240, 360, 540, 720, 1,080, and 1,440 minutes after drug administration. Serum buprenorphine concentrations were determined by use of double-antibody radioimmunoassay. Data were subjected to noncompartmental analysis with area under the time-concentration curve to infinity (AUC) and area under the first moment curve calculated to infinity by use of a log-linear trapezoidal model. Other kinetic variables included terminal rate constant (kel) and elimination half-life (t1/2), plasma clearance (Cl), volume of distribution at steady state (Vdss), and mean residence time (MRT). Time to maximal concentration (Tmax) and maximal serum concentration (Cmax) were measured.
Results—Median (range) values for Tmax and MRT were 2 minutes (2 to 5 minutes) and 264 minutes (199 to 600 minutes), respectively. Harmonic mean and pseudo SD for t1/2 were 270 ± 130 minutes; mean ± SD values for remaining pharmacokinetic variables were as follows: Cmax, 14 ± 2.6 ng/mL; AUC, 3,082 ± 1,047 ng•min/mL; Vdss, 1.59 ± 0.285 L/kg; Cl, 5.4 ± 1.9 mL/min/kg; and, kel, 0.0026 ± 0.0,012.
Conclusions and Clinical Relevance—Pharmacokinetic variables of buprenorphine reported here differed from those previously reported for dogs. Wide variations in individual t1/2 values suggested that dosing intervals be based on assessment of pain status rather than prescribed dosing intervals.
Objective—To determine the pharmacokinetics and hemodynamic effects of trazodone after IV and oral administration in dogs and bioavailability after oral administration.
Animals—6 adult Beagles.
Procedures—Dogs received trazodone HCl (8 mg/kg) orally and IV in a randomized controlled crossover design. Blood samples were collected at various times after administration. Heart rates and indirectly measured blood pressures of dogs and plasma concentrations and pharmacokinetics of trazodone were determined.
Results—Following IV administration, the mean ± SD elimination half-life, apparent volume of distribution, and plasma total body clearance were 169 ± 53 minutes, 2.53 ± 0.47 L/kg, and 11.15 ± 3.56 mL/min/kg, respectively. Following oral administration, the mean ± SD elimination half-life and absolute bioavailability were 166 ± 47 minutes and 84.6 ± 13.2%, respectively. Maximum plasma concentration following oral administration was 1.3 ± 0.5 μ/mL, and time to maximum plasma concentration was 445 ± 271 minutes. After IV administration, all dogs immediately developed transient tachycardia (184.3 ± 8.0 beats/min), and 3 of 6 dogs developed aggression. Increase in heart rate was significantly associated with increase in plasma drug concentration following IV administration.
Conclusions and Clinical Relevance—Results of this study indicated oral administration of trazodone resulted in acceptable absolute bioavailability, with substantial variability in time to maximum plasma concentration. Individualized approaches in dosing intervals may be necessary for dogs receiving oral trazodone. An orally administered dose of 8 mg/kg was well tolerated in dogs; IV administration of a dose of 8 mg/kg caused substantial adverse effects, including tachycardia and behavior disinhibition.
OBJECTIVE To identify risk factors associated with surgical site infection (SSI) in dogs following tibial plateau leveling osteotomy (TPLO).
DESIGN Retrospective cohort study.
ANIMALS 320 dogs that underwent unilateral or bilateral TPLO (n = 405 procedures) between 2007 and 2015 and were reexamined by a veterinarian at least once ≥ 8 weeks after the procedure.
PROCEDURES Data were extracted from medical records regarding signalment, TPLO procedure details, medical history of dermatitis, and SSI status. Logistic regression was performed to identify factors associated with SSI development.
RESULTS An SSI developed following 34 (8.4%; 95% confidence interval [CI], 6.1% to 11.5%) procedures. Prophylactic antimicrobial administration was provided following 36.8% (n = 149) of procedures. For 71 (17.5%) procedures, the dog had dermatitis at the time of surgery; 12 of these procedures involved dermatitis at the surgical site. The incidence of SSI following the 12 procedures for dogs with dermatitis at the surgical site was 16.7% (2/12 [95% CI, 3.3% to 54.3%]) and was 10.2% (6/59 [95% CI, 4.5% to 21.3%]) for dogs with dermatitis elsewhere; however, these differences in incidence were not significant. On multivariable analysis, German Shepherd Dogs (vs other breeds), meniscectomy (vs no meniscectomy), and attending surgeon having performed ≤ 20 (vs > 20) procedures during the study period were associated with increased odds of SSI.
CONCLUSIONS AND CLINICAL RELEVANCE SSI following TPLO was associated with the German Shepherd breed, meniscectomy, and surgeon. Prospective studies are needed to investigate the mechanisms underlying these associations.
Objective—To estimate heritabilities and genetic correlations among 4 traits of hip joints (distraction index [DI], dorsolateral subluxation [DLS] score, Norberg angle [NA], and extended–hip joint radiograph [EHR] score) and to derive the breeding values for these traits in dogs.
Animals—2,716 dogs of 17 breeds (1,551 dogs in which at least 1 hip joint trait was measured).
Procedures—The NA was measured, and an EHR score was assigned. Hip joint radiographs were obtained from some dogs to allow calculation of the DI and DLS score. Heritabilities, genetic correlations, and breeding values among the DI, DLS score, NA, and EHR score were calculated by use of a set of multiple-trait, derivative-free, restricted maximum likelihood computer programs.
Results—Among 2,716 dogs, 1,411 (52%) had an estimated inbreeding coefficient of 0%; the remaining dogs had a mean inbreeding coefficient of 6.21%. Estimated heritabilities were 0.61, 0.54, 0.73, and 0.76 for the DI, DLS score, NA, and EHR score, respectively. The EHR score was highly genetically correlated with the NA (r = −0.89) and was moderately genetically correlated with the DI (r = 0.69) and DLS score (r = −0.70). The NA was moderately genetically correlated with the DI (r = −0.69) and DLS score (r = 0.58). Genetic correlation between the DI and DLS score was high (r = −0.91).
Conclusions and Clinical Relevance—Establishment of a selection index that makes use of breeding values jointly estimated from the DI, DLS score, NA, and EHR score should enhance breeding programs to reduce the incidence of hip dysplasia in dogs.
Objective—To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs.
Procedures—Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever–Greyhound crossbreeds.
Results—The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage.
Conclusions and Clinical Relevance—The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.