Use of Body Surface Area to Calculate Chemotherapeutic Drug Dose in Dogs: II. Limitations Imposed by Pharmacokinetic Factors

Anticancer drug dosages that specify the maximum dose and minimum dosing interval that are tolerated in a population of dogs are commonly recommended. Because the differences between the effective and toxic doses of most cancer chemotherapeutics is slight, it is important to achieve therapeutic concentrations in tumor tissues at the same time that concentrations in nontarget tissues are minimized. In order to determine the dosage regimen that will most likely accomplish these goals, similar drug concentrations must be achieved in all patients dosed according to a specific regimen. Dosing based on body surface area (BSA) is generally used in an effort to normalize drug concentrations. This is because it is well recognized that measures of many physiologic parameters that are responsible for drug disposition, including renal function and energy expenditure, can be normalized by use of BSA. However, there is substantial evidence that drug disposition is not always proportional to BSA. Differences in distribution, metabolism, and excretion pathways may preclude dose extrapolation among species or among individuals within a species based on BSA. Moreover, genetic differences in drug metabolism are well recognized in humans and in laboratory animals, and it is likely that similar differences exist among breeds of dogs. A review of the pharmacokinetic disposition of several cancer chemotherapeutics suggests that studies are needed to determine the most effective method to achieve equivalent anticancer drug concentrations in diverse veterinary patients.     

Single-Drug Chemotherapy of Canine Transmissible Venereal Tumor With Cyclophosphamide, Methotrexate, or Vincristine

During a 21-month period, 48 dogs with spontaneous canine transmissible venereal tumor (clinical stage, T1-T3) were presented to the Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria, and were divided into one control and four treatment groups to test the efficacy of single-agent chemotherapeutic drugs. The dogs were not randomly assigned to groups because each chemotherapeutic agent was not continuously available during the test period. Group I consisted of four dogs that received oral cyclophosphamide (50 mg/M2 body surface area [BSA]) on the first four days for six weeks. No therapeutic response was noted in any of the four dogs. Group II consisted of ten dogs that received intravenous (IV) cyclophosphamide (50 mg/M2 BSA) for four consecutive days per week for six weeks. Two of the ten had a partial remission. Group III consisted of eight dogs that received oral methotrexate (2.5 mg/M2 BSA) every other day for six weeks. No therapeutic response was noted in any of the eight dogs. Group IV consisted of 20 dogs that were administered IV vincristine sulfate (0.5 mg/M2 BSA) weekly until a response was noted. Complete remission occurred in each of the 20 dogs. One dog had recurrence within 12 months. Group V was the untreated control group, consisting of six dogs among which no spontaneous remission was seen. Instead, tumor progression was noted. Adverse responses to medication, anorexia, vomiting, diarrhea, and weight loss were seen only with dogs treated with cyclophosphamide and methotrexate.     

Bone marrow necrosis in dogs: 34 cases (1996-2004)

OBJECTIVE: To identify the incidence, potential causes, and clinical and clinicopathologic features of bone marrow necrosis in dogs. DESIGN: Retrospective study. ANIMALS: 34 client-owned dogs. PROCEDURES: Reports of cytologic examinations of bone marrow specimens performed between 1996 and 2004 were reviewed. All reports that indicated the presence of necrosis, stromal disruption, phagocytic macrophages, individual cell necrosis, or myelofibrosis were evaluated further. RESULTS: Of 609 reports of bone marrow evaluations performed during the study period, 34 (5.6%) had evidence of bone marrow necrosis. Nine dogs had no evidence of associated diseases or drug or toxin exposure, and 25 dogs had associated disease conditions or drug exposures. All 9 dogs with idiopathic bone marrow necrosis were anemic (mean Hct, 14%), but only 3 had neutropenia, and 3 had thrombocytopenia. All 9 had myelofibrosis. Of the 25 dogs with associated disease conditions or drug exposures, only 14 (56%) had anemia (mean Hct, 33%). In addition, 14 (56%) had neutropenia and 18 (72%) had thrombocytopenia. Only 10 (40%) had myelofibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that bone marrow necrosis may be common in dogs with hematologic disorders. In most dogs, bone marrow necrosis was associated with an underlying disease condition or drug exposure, but idiopathic bone marrow necrosis was also identified. Disease conditions that should increase suspicion of possible bone marrow necrosis include sepsis, lymphosarcoma, and systemic lupus erythematosus; drug exposures that should increase suspicion of possible bone marrow necrosis include chemotherapeutic agents, phenobarbital, carprofen, metronidazole, and mitotane.     

Increased risk of select glucocorticoid adverse events in dogs of higher body weight

There are limited data on glucocorticoid treatment in dogs. The purpose of this study was to investigate whether dogs of higher body weight experienced more adverse events when receiving glucocorticoid therapy. Data pertaining to glucocorticoid therapy was abstracted from the records of 61 dogs that were prescribed glucocorticoids for treatment of immune-mediated thrombocytopenia or hemolytic anemia from 2014 to 2019. The odds of developing muscle atrophy and polyphagia during therapy were increased by 30% for each 5 kg of additional body weight. Almost half of the dogs (44.3%) fluctuated > 15% from baseline weight during therapy. Dogs whose body condition scored as above ideal were at increased risk (odds ratio = 4.2) for being diagnosed with urinary tract infection. Our findings suggest that standard linear glucocorticoid dosing may place higher body weight dogs at increased risk of developing adverse events. Accelerated glucocorticoid tapering and/or alternative dosing schemes in dogs with higher body weights may be prudent in efforts to improve tolerance and client compliance.     

THE USE OF M-MODE ECHOCARDIOGRAPHY IN DETERMINING CARDIAC OUTPUT IN DOGS WITH NORMAL, LOW, AND HIGH OUTPUT STATES: COMPARISON TO THERMODILUTION METHOD

The utility of M-mode echocardiographic determination of left ventricular volume and cardiac output was evaluated by comparing four commonly used formulae for ventricular volume, derived from end-systolic (ESD) and end-diastolic (EDD) ventricular dimensions. Cardiac index (CI) was calculated by the following formulae, where HR = heart rate and BSA = body surface area (M²): 1. (EDD³- ESD³) * HR/BSA; 2. (0.85 * EDD³ - 1.2 *ESD³) * HR/BSA; 3. (EDD^3.16 - ESD^3.16) * HR/BSA; and 4. {[7/(2.4 + EDD)] * [EDD³] - [7/(2.4 + ESD)] * [ESD³)}* HR/BSA. Cardiac index, obtained invasively by thermodilution, was compared to values determined echocardiographically in normal dogs (Group 1) and in three states of altered cardiac function: after positive inotropic stimulation with graded doses (0,5,10, and 15 μg/kg/min) of intravenous dobutamine (Group 2); with experimentally induced heartworm disease (Group 3); and with spontaneous dilated cardiomyopathy (Group 4). Cardiac index, determined echocardiographically, was plotted against CI, determined with thermodilution, and regression equations calculated. In Group 1 (n = 15), a significant relationship (P < 0.01) was observed with each of the four formulae (r²= 0.54-0.68), however, individual estimates of CI were often inaccurate. With inotropic stimulation (Group 2;3 normal dogs, n = 12 data points), the relationship was significant (P < 0.05), but the coefficients of determination were less than in the unstimulated normal dogs (r²= 0.41-0.47). No significant relationship was seen between CI, determined echocardiographically and CI, determined by thermodilution, when overt cardiac disease was present (Groups 3 and 4; n = 7 and 13, r²= 0.13-0.21, respectively). Specific formulae were evaluated for accuracy by comparing their coefficients of determination and their ability to predict mean and individual measured CI. Using the paired Student's t-test, CI determined noninvasively were shown to differ significantly (P < 0.05) between methods and between formulae in many instances. No one formula was found to be consistently more accurate than the others. We conclude that, in normal dogs, while echocardiographic estimation of CI is significantly related to CI measured with thermodilution, individual variation diminishes clinical utility. However, this noninvasive technique should prove useful in comparing populations with minimal or no cardiac dysfunction. Secondly, the relationship is diminished, but not lost, after inotropic stimulation. M-mode echocardiographic estimation of CI offers little promise for accurate assessment of cardiac performance in cardiac disease states. Lastly, although none of the four formulae for CI compared herein were found to be consistently superior to the other three, formulae 3 and 4 appear to be most useful in estimating CI in normal dogs.     

The use of concentrated bovine serum albumin in canines.

In humans it has been estimated that for each 2.5 g L^–1 decrease in serum albumin, risk of death increases by 24–56%. Clinical impression suggests this may be similar in veterinary patients. Species‐specific albumin (plasma) is often unavailable and concentrated solutions are not. Our experience using 25% human serum albumin (HSA) in critically ill dogs suggests a positive effect (results submitted), however it is expensive. Bovine serum albumin (BSA) may be a more cost effective and readily available alternative. The purpose of this study was to assess the immediate and long‐term safety of an intravenous dose (500 mg kg^–1) of bovine albumin administered to healthy dogs. Ten mature dogs (eight males, two females, 28 ± 6 kg) were to receive BSA (250 mg mL^–1) twice (BSA1 and BSA2) with 14 days between treatments. Temperature, blood pressure, and pulse and respiration rate were continuously monitored to identify a reaction to BSA. All dogs received BSA1. One dog immediately developed mild urticaria and pruritus, otherwise the infusion was well tolerated. No immediate reaction was noted in the other nine dogs. Two dogs received BSA2. One dog developed a mild immediate reaction similar to that occurring with BSA1, and one dog (the dog immediately reacting to BSA1) developed a severe anaphylactic reaction. Due to these reactions, no other dogs received BSA2. During a two‐week observation of the remaining eight dogs given BSA1, five developed a mild or severe generalized type‐III hypersensitivity reaction. The dog experiencing a mild reaction during BSA2 administration also developed a generalized type‐III hypersensitivity reaction. Delayed reactions occurred 15 ± 2.7 days after BSA exposure. Three dogs did not develop a reaction. All reacting dogs recovered fully. The severity of reactions, and the number of dogs affected, suggests prior (natural) exposure and immunological sensitization to bovine albumin. Bovine serum albumin is not suitable for therapeutic use in dogs.     

Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs

In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.     

Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma

Background: Cyclophosphamide is an alkylating chemotherapeutic drug administered IV or PO. It is currently assumed that exposure to the active metabolite, 4‐hydroxycyclophosphamide (4‐OHCP), is the same with either route of administration.

Objectives:

To characterize the pharmacokinetics of cyclophosphamide and 4‐OHCP in dogs with lymphoma when administered PO or IV. Animals: Sixteen client‐owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide IV and 8 received it PO. Methods: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4‐OHCP with mass spectrometry and liquid chromatography. Results: Drug exposure to cyclophosphamide measured by area under the curve (AUC)_0–inf is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P‐value < .05). No difference in drug exposure to 4‐OHCP was detected after IV (1.66 ± 0.36 μg/h/mL) or PO (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide. Conclusions and Clinical Importance: Drug exposure to the active metabolite 4‐OHCP is equivalent after administration of cyclophosphamide either PO or IV.     

Investigation of the effect of pamidronate disodium on the in vitro viability of osteosarcoma cells from dogs

OBJECTIVE: To determine the effect of pamidronate disodium on the in vitro viability of osteosarcoma cells and non-neoplastic cells from dogs. SAMPLE POPULATION: 3 osteosarcoma and 1 fibroblast cell lines derived from dogs. PROCEDURE: Cell counts and cell viability assays were performed in cultures of osteosarcoma cells (POS, HMPOS, and COS31 cell lines) and fibroblasts after 24, 48, and 72 hours of incubation with pamidronate at concentrations of 0.001 to 1000 microM or with no drug (control treatment). Percentage viability was determined in cell samples for each concentration of pamidronate and each incubation time. A DNA fragmentation analysis was performed to assess bisphosphonate-induced apoptosis. RESULTS: Osteosarcoma cell viability decreased significantly in a concentration- and time-dependent manner at pamidronate concentrations ranging from 100 to 1000 microM, most consistently after 48 and 72 hours' exposure. In treated osteosarcoma cells, the lowest percentage cell viability was 34% (detected after 72 hours' exposure to 1000 microM pamidronate). Conversely, 72 hours' exposure to 1000 microM pamidronate did not significantly reduce fibroblast viability (the lowest percentage viability was 76%). After 72 hours of exposure, pamidronate did not cause DNA fragmentation in POS or HMPOS cells. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that pamidronate may have the potential to inhibit osteosarcoma growth in dogs, possibly through a nonapoptotic mechanism. The clinical relevance of these in vitro findings remains to be determined, but administration of pamidronate may potentially be indicated as an adjuvant treatment in chemotherapeutic protocols used in dogs.     

Fluoroquinolone-induced retinal degeneration in cats

Although the exact mechanism of fluoroquinolone-induced retinal degeneration in cats remains to be elucidated, it appears from the literature that a similar retinal degeneration can be reproduced from either direct intravitreal injection of high concentrations of drug or exposure to UVA light and drug in laboratory animals. (19,25) The fluoroquinolone molecular structure is also similar structurally to other drugs that are known to directly induce retinal degeneration, including the cinchona alkaloids and halogenated hydroquinolones. Experimental evidence suggests that both the parent compound and its breakdown products via metabolism and photodegradation are active inducers of retinal degeneration. (18,25) Development of toxicoses also appears to be dependent on the maximum concentration of active drug, metabolite, or both reaching the retina over time. (18) Evaluation of the literature suggests that risk factors predisposing cats to fluoroquinolone-induced retinal degeneration may include the following: 1) large doses or plasma concentrations of drug, 2) rapid IV infusion of the antibiotic, 3) prolonged courses of treatment, and 4) age. Theoretically, other risk factors may also be involved including the following: 1) prolonged exposure to UVA light while the antibiotic is being administered, 2) drug interactions, and 3) drug or metabolite accumulation from altered metabolism or reduced elimination. To date, there are no published reports suggesting that the dose of fluoroquinolones should be reduced in geriatric cats or those with renal or hepatic failure. However, accumulation of fluoroquinolone metabolites in dogs and of the parent compound in humans with decreased renal function has been reported. (8-10) In humans with decreased renal function has been reported. (8-10) humans, fluoroquinolone doses are typically decreased in response to the degree of renal impairment. (28) In general, all fluoroquinolone antibiotics should be reserved for severe or recurrent infections, and whenever possible their use should be based on results whenever possible their use should be based on results of culture and susceptibility tests. When indicated, the fluoroquinolones, including enrofloxacin, can be used with limited risk of developing retinal degeneration in cats, provided the manufacturer's guidelines are adhered to and dose reduction is considered in geriatric cats or those with renal impairment. Dosing on renal impairment. Dosing on exact body weight using split dosing (2.5 mg/kg, PO, q 12 h) and avoidance of rapid IV infusions, and drug interactions may help to reduce the risk of retinal degeneration in some cases. Furthermore, monitoring cats for mydriasis and avoidance of UVA light while undergoing treatment may also be of benefit. Further evaluation of the pharmacokinetics of enrofloxacin and the other fluoroquinolones is required in geriatric cats or those with mild to moderate renal or liver impairment to determine whether drug accumulation, elevated peak concentrations of drug, or both may be occurring in this subset of cats. Therapeutic monitoring of drug concentrations may not always be feasible because of time and cost, but renal panels with dose or frequency reduction in response to the degree of renal impairment and the site and severity of infection may help to reduce retinal toxicosis.     

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs

This study investigated the pharmacokinetics of a human-labeled oral morphine formulation consisting of both immediate and extended release components in dogs. In a randomized design, 14 dogs were administered either 1 or 2 mg/kg morphine orally. Blood samples were collected up to 24 h post drug administration. Plasma concentrations of morphine were measured using high-pressure liquid chromatography with electrochemical coulometric detection. For both groups, maximal concentration occurred at 3 h post drug administration followed by a gradual decrease in morphine concentration over 24 h. There was substantial variability in morphine concentrations among dogs. The higher dose group produced a greater exposure (higher area-under-the-curve), higher peak concentration, longer half-life and a shorter time to peak concentration ( t _max). The specific oral morphine formulation used in this study produced sustained plasma morphine concentrations over 24 h compared with previous intravenous dosing and immediate-release oral morphine studies. However, the low morphine plasma concentrations and high variability produced from this formulation, suggest that the clinical application of this formulation at the doses evaluated in this study are limited.     

Dosing regimen and hematologic effects of pentoxifylline and its active metabolites in normal dogs

The disposition of pentoxifylline and two of its active metabolites (metabolite 1 [M1] and metabolite 5 [M5]) were studied following i.v. (8 mg/kg) and p.o. (30 mg/kg) administration to eight normal dogs using a randomized crossover design. Blood samples were collected at fixed time intervals after drug administration for determination of drug concentrations, platelet aggregation, and plasma fibrinogen. Complete blood counts, serum chemistry profiles, fibrinogen, and urinalysis were monitored at the beginning and end of each phase of the study (p.o. versus i.v. administration). Pentoxifylline was readily metabolized and bioavailable (50% +/- 26%). Both M1 and M5 were present throughout the study, with M5 predominating. Human drug therapeutic concentrations (1,000 ng/ml) were present for 170 +/- 24 minutes following i.v. administration and 510 +/- 85 minutes after p.o. dosing. These findings suggest that a 12-hour dosing regimen is appropriate. None of the dogs experienced any adverse effects after pentoxifylline administration. The lack of hematologic effects suggests that the immunologic effects of pentoxifylline may be of more importance in dogs.     

Cyclosporine A affects the in vitro expression of T cell activation-related molecules and cytokines in dogs

Cyclosporine is a powerful immunosuppressive drug that is being used with increasing frequency to treat a wide range of immune-mediated diseases in the dog. To date, ideal dosing protocols that will achieve immunosuppression with cyclosporine in dogs remain unclear, and standard methods that can measure effectiveness of immunosuppression have not been established. The aim of our study was to evaluate the effects of in vitro cyclosporine exposure on a panel of molecules expressed by activated T cells to ascertain their potential as biomarkers of immunosuppression in dogs. Blood was drawn from six healthy dogs, and peripheral blood mononuclear cells (PBMC) were isolated and activated. Half of the cells were incubated with 200 ng/mL cyclosporine prior to activation, and the other half were not exposed to cyclosporine. Samples were analyzed using flow cytometry, and the expression of intracellular cytokines IL-2, IL-4, and IFN-γ was evaluated after 6, 12, and 24h of drug exposure. Each cytokine exhibited a time-dependent suppression profile, and all but two samples activated in the presence of cyclosporine showed lower cytokine expression than untreated controls. We also evaluated the expression of the surface T cell activation molecules CD25 and CD95 by flow cytometry after 36 h of drug exposure. Expression of these surface molecules decreased significantly when activated in the presence of cyclosporine. Our results suggest that suppressed expression of the markers related to T cell activation could potentially be utilized as an indicator of the efficacy of cyclosporine therapy in dogs.     

Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing

The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg?kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high‐performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC_0–24: minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 μg/mL, which is lower than the recommended target of 20–25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13–30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.     

Incidence of prolonged prothrombin time in dogs following gastrointestinal decontamination for acute anticoagulant rodenticide ingestion

Objective: To determine the effect of gastrointestinal (GI) decontamination on the incidence of prolonged prothrombin time (PT) in dogs after anticoagulant rodenticide ingestion. Design: Retrospective study. Setting: Urban emergency room. Animals: One hundred and fifty‐one client‐owned dogs. Measurements: Dogs presented to the emergency room within 6 hours of ingestion of an anticoagulant rodenticide and had a PT measured within 2–6 days of toxicant ingestion before initiating vitamin K therapy were included. Dogs were categorized as treated or untreated based on the institution of vitamin K therapy following PT testing. The signalment, body weight, type of rodenticide ingested, time elapsed between ingestion and initial presentation, method(s) of GI decontamination, and the times elapsed between both toxicant ingestion and initial hospital presentation until determination of PT were recorded. The PT results were recorded as well as any treatment received following the recheck examination. Any reported incidents of bleeding or untoward effects between exposure and reexamination were recorded. Main results: Of 151 dogs, only 11 dogs (8.3%) developed prolonged PT requiring vitamin K supplementation. None of the 11 dogs with prolonged PTs exhibited signs of bleeding or required transfusion therapy. No differences in age, weight, or time elapsed between treated and untreated patients were found. Conclusions: The incidence of prolonged PT is low in dogs receiving GI decontamination within 6 hours of anticoagulant rodenticide ingestion. Delaying vitamin K therapy until a PT has been assessed 48–72 hours after initial exposure appears to be safe and sensitive in dogs following anticoagulant rodenticide ingestion.     

Allometric scaling of M-mode cardiac measurements in normal adult dogs

Indices for M-mode measurements in dogs usually have been based on the assumption that a linear relationship exists between these measurements and body weight (BW) or body surface area (BSA). The relationships between the geometry of 3-dimensional objects do not support this assumption. The purposes of this study were to retrospectively examine M-mode data from a large number of dogs of varying sizes and breeds that were examined by a large number of ultrasonographers, to use the allometric equation to determine the appropriate BW exponent required to predict these cardiac dimensions, and to determine normal mean values and prediction intervals for common M-mode variables. Linear regression analyses of data from 494 dogs (2.2-95 kg) revealed a good correlation between M-mode measurements and BW after logarithmic transformation of the data (r2 = .55-.88). Most variables were most closely related to an index of body length, BW(1/3), although the exponent that best predicted diastolic and systolic left ventricular wall thicknesses was closer to 0.25. No variable indexed well to BW or BSA. With these data, appropriate mean values and prediction intervals were calculated for normal dogs, allowing veterinarians to correctly and appropriately index M-mode values. The equations developed from this study appear to be applicable to adult dogs of most breeds.     

Complications following thiacetarsamide sodium therapy in Louisiana dogs with naturally-occurring heartworm disease

Four hundred and sixteen dogs with naturally-occurring heartworm disease were evaluated for complications following thiacetarsamide sodium therapy. Of these, 109 dogs (26.2%) experienced complications. Increased lung sounds was the most commonly seen complication, followed by fever and coughing. In dogs with complications, 83.5% of them presented without clinical evidence of pulmonary thromboembolism or heart failure. There were no statistically significant differences between the age, sex, breed and body size of dogs that experienced complications following thiacetarsamide therapy and dogs that did not. Complications were most frequently seen 5 to 9 days following thiacetarsamide therapy although some dogs experienced initial complications as late as 28 days. Thirty-three of 109 dogs (33.0%) with complications responded to exercise restriction. The remaining 76 dogs with complications prior to or following thiacetarsamide required adjunct drug therapy. Of these, 35 dogs responded favorably to anti-inflammatory doses of prednisolone or prednisone. Five dogs died or were euthanatized because of the complications experienced. Eighteen of 416 dogs (4.3%) presented with clinical evidence of pulmonary thromboembolism or heart failure prior to the thiacetarsamide therapy. All 18 dogs experienced complications in spite of adjunct drug therapy and exercise restriction prior to, during, and following thiacetarsamide therapy. Survival rate following resolution of the thiacetarsamide-induced complications was greater than 98%.