Pharmacokinetics of voriconazole after oral and intravenous administration to horses

OBJECTIVE: To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. ANIMALS: 6 adult horses. PROCEDURES: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. RESULTS: Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration 相似文献   

Characterization of primary pulmonary adenosquamous carcinoma‐associated pleural effusion

A 10‐year‐old, female spayed Shih Tzu was presented due to weight loss, increased respiratory effort and lethargy, determined to be secondary to a congenital para‐esophageal diaphragmatic defect with partial herniation of the stomach and spleen. Four days following reduction surgery of the displaced abdominal organs thoracic effusion developed. Thoracic fluid evaluation revealed a cell‐rich, protein‐poor modified transudate with neutrophils, reactive mesothelial cells, and atypical epitheloid cells which occasionally appeared to be keratinizing, consistent with neoplastic exfoliation. Thoracic effusion recurred 2 days later, with similar characteristics as the initial sample. Computed tomography (CT) indicated consolidation and displacement of the right middle and accessory lung lobes. Exploratory thoracic surgery demonstrated a thickened, hyperemic right middle lung lobe, and thickened pericardial diaphragmatic ligament. Histologic evaluation of these tissues identified a primary pulmonary adenosquamous carcinoma with intravascular and pleural invasion. Based on these cytologic, histologic, and clinical findings, we conclude that primary pulmonary carcinomas may involve superficial thoracic structures and exfoliate into a thoracic effusion.     

Clinical and magnetic resonance imaging findings in 92 cats with clinical signs of spinal cord disease

Medical records of 92 cats presented with clinical signs of spinal cord disease, which had undergone magnetic resonance imaging (MRI), were reviewed. The cats were grouped into seven categories based upon the diagnosis suggested by results of MRI, cerebrospinal fluid analysis and other diagnostic procedures: neoplastic (n=25), inflammatory or infectious (n=13), traumatic (n=8), vascular (n=6), degenerative (n=5), anomalous (n=3) and those with an unremarkable MRI (n=32). There were two independent predictors of abnormal MRI findings: severity of clinical signs and presence of spinal pain. Abnormal MRI findings and speed of onset of disease were significantly associated with survival. For the 32 cats with unremarkable MRI findings, only nine died due to spinal disease and, therefore, the median survival time (MST) was not reached (lower 95% confidence interval (CI)=970 days). For the 60 cats with abnormal MRI findings, 37 died due to their disease and the MST was 138 days (95% CI: 7-807).     

What is your diagnosis? Marked hyperchloremia in a dog

Abstract: A 5‐year‐old neutered male Cavalier King Charles Spaniel was evaluated for a 3‐week history of progressive paresis. The dog had been receiving potassium citrate capsules to acidify urine for the past 2 years because of an earlier history of urolithiasis. Results of neurologic examination, spinal cord radiography, and magnetic resonance imaging of the skull and spinal cord revealed no lesions that could have accounted for the neurologic signs. The main abnormalities on a clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference interval 108–122 mmol/L) and an anion gap of ?50.4 mmol/L (reference interval 16.3–28.6 mmol/L). Because of the severe hyperchloremia, serum bromide concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which had been compounded at a local pharmacy, yielded a mean bromide concentration of 239 mg/capsule. Administration of the capsules was discontinued and there was rapid resolution of the dog's neurologic signs. This case of extreme bromide toxicity, which apparently resulted from inadvertent use of bromide instead of citrate at the pharmacy, illustrates the importance of knowing common interferents with analyte methodologies and of pursing logical additional diagnostic tests based on clinical and laboratory evidence, even when a patient's history appears to rule out a potential etiology.     

Ultrasonographic findings in dogs and cats with oxalate nephrosis attributed to ethylene glycol intoxication: 15 cases (1984-1988)

Renal ultrasonographic findings in 12 dogs and 3 cats determined to have oxalate nephrosis presumed to be secondary to ethylene glycol intoxication were examined. Ultrasonographic changes varied from mild to marked increases in renal cortical echogenicity. A pattern of greater than normal cortical and medullary echogenicity with persistence of areas of lesser echo intensity at the corticomedullary junction and central medullary regions was observed. This pattern, termed the halo sign, was recognized in 7 dogs and 1 cat concurrent with the development of clinical anuria. Ultrasonographic patterns in these clinical cases were similar to those observed in a previous study of dogs with experimentally induced ethylene glycol nephrosis. Ultrasonographic findings were not considered pathognomonic of ethylene glycol nephrosis. Due to the high death rate reported in the cases surveyed, detection of ultrasonographic changes was considered to warrant a guarded to poor prognosis. Because of the association of the halo sign with anuria, its detection was considered to warrant a grave prognosis.     

Prevalence of serum antibodies against Bartonella species in the serum of cats with or without uveitis

Bartonella henselae has been implicated as a causative agent of chronic uveitis in people and in some cats. The objective of this study was to determine whether Bartonella species seroprevalence or titer magnitude varies among cats with uveitis, cats without ocular diseases recorded and healthy cats, while controlling for age and risk of flea exposure based on state of residence. There was no difference in seroprevalence rates or titer magnitude between cats with uveitis and cats with non-ocular diseases. Healthy cats were more likely to be seropositive for Bartonella species than cats with uveitis. The median Bartonella species titer was 1:64 for all groups, although healthy cats were more likely to have higher titers than cats with uveitis and cats with non-ocular disease. The results suggest that serum antibody tests alone cannot be used to document clinical uveitis associated with Bartonella species infection.     

Packed red blood cell transfusions in dogs with gastrointestinal hemorrhage: 55 cases (1999-2001)

Fifty-five dogs received packed red blood cell (PRBC) transfusions for gastrointestinal (GI) hemorrhage during a 26-month period (1999 to 2001), accounting for 11.7% of the PRBC transfusions in that time. Thirty-nine (61%) dogs had an intestinal pathology (primary or secondary) as the cause of GI hemorrhage, including intestinal masses, gastroenteritis, hepatic disease, and renal disease. Nonsteroidal and steroidal anti-inflammatory drug use was found frequently in dogs with GI hemorrhage. Sixteen (39%) dogs were identified as having immune-mediated thrombocytopenia (IMT) and associated GI hemorrhage. Dogs with IMT received more transfusions of PRBC than nonIMT dogs (P<0.03) and received a significantly larger total volume of PRBC (P<0.01) during hospitalization.     

A case of methicillin-resistant Staphylococcus pseudintermedius (MRSP) pyoderma in a Labrador retriever dog

An 8-year-old, neutered male Labrador retriever dog with generalized pruritis had a history of recurring atopic dermatitis and superficial pyoderma. Cocci and yeast were found on cytology and methicillin-resistant Staphylococcus pseudintermedius was cultured. A regimen of marbofloxacin, dexamethasone, ketoconazole, and cyclosporine in addition to bathing with 2% chlorhexidine shampoo resulted in marked improvement.