The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (V ) were 0.15 (0.13-0.18) L hr kg and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C ; median: 0.72, range: 0.55-0.93 μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas.
Amoxicillin was administered as a single subcutaneous injection at 12.5 mg/kg to four koalas and changes in amoxicillin plasma concentrations over 24 hr were quantified. Amoxicillin had a relatively low average ± SD maximum plasma concentration (Cmax) of 1.72 ± 0.47 µg/ml; at an average ± SD time to reach Cmax (Tmax) of 2.25 ± 1.26 hr, and an elimination half‐life of 4.38 ± 2.40 hr. The pharmacokinetic profile indicated relatively poor subcutaneous absorption. A metabolite was also identified, likely associated with glucuronic acid conjugation. Bacterial growth inhibition assays demonstrated that all plasma samples other than t = 0 hr, inhibited the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 to some extent. Calculated pharmacokinetic indices were used to predict whether this dose could attain a plasma concentration to inhibit some susceptible Gram‐negative and Gram‐positive pathogens. It was predicted that a twice daily dose of 12.5 mg/kg would be efficacious to inhibit susceptible bacteria with an amoxicillin minimum inhibitory concentration (MIC) ≤ 0.75 µg/ml such as susceptible Bordetella bronchiseptica, E. coli, Staphylococcus spp. and Streptococcus spp. pathogens.
Background Cefovecin has a long duration of antibiotic activity in cats and dogs, somewhat attributable to its high plasma protein binding. Aims To determine the cefovecin binding to plasma proteins in vitro in selected Australian marsupials and to quantify the change in cetovecin concentration over time following subcutaneous injection in koalas. Methods and results Various cefovecin concentrations were incubated with plasma and quantified using HPLC. The median (range) bound percentages when 10 μg/mL of cefovecin was incubated with plasma were 11.1 (4.1–20.4) in the plasma of the Tasmanian devil, 12.7 (5.8–17.3) in the koala, 18.9 (14.6–38.0) in the eastern grey kangaroo, 16.9 (15.7–30.2) in the common brush‐tailed possum, 37.6 (25.3–42.3) in the eastern ring‐tailed possum and 36.4 (35.0–38.3) in the red kangaroo, suggesting that cefovecin may have a shorter duration of action in these species than in cats and dogs. Cefovecin binding to plasma proteins in thawed, frozen equine plasma was also undertaken for assay quality control and the median (range) plasma protein binding (at 10 μg/mL) was 95.6% (94.9–96.6%). Cefovecin was also administered to six koalas at 8 mg/kg subcutaneously and serial blood samples were collected at 3, 6, 24, 48, 72, 96 h thereafter. Cefovecin plasma concentrations were not quantifiable in four koalas and in the other two, the mean plasma concentration at t = 3 h was 1.04 ± 0.01 μg/mL. Conclusion Because of the limited pharmacokinetic data generated, no further pharmacokinetic analysis was performed; however, a single injected bolus of cefovecin is likely to have a short duration of action in koalas (hours, rather than days).
Background: Due to its non-specific symptoms, pulmonary arterial hypertension (PAH) is difficult to diagnose via non-invasive methods. Various diagnostic tests are required to evaluate PAH patients. The increased diameter of the main pulmonary artery in computed tomography (CT) imaging represents a high probability of PAH. Moreover, N-terminal pro B-type natriuretic peptide (NT-proBNP) and pro B-type natriuretic peptide (proBNP) can be considered as prognostic predictors in patients with PAH. Objectives: This study aimed to evaluate the correlation of CT-based main pulmonary artery diameter (MPAD) and the serum level of NT-proBNP (as a strong pro-inflammatory factor) with the severity of PAH in echocardiography among patients with PAH. Patients and Methods: In this cross-sectional study, a total of 63 hospitalized patients with PAH due to chronic obstructive pulmonary disease were recruited from 2019 to 2020 after initial evaluations and collection of serum NT-proBNP measurements and echocardiographic findings. On the chest CT scans, the largest diameter of the pulmonary artery trunk was determined, and then, correlation of CT-based MPAD with both PAH severity on echocardiography and NT-proBNP level in patients with PAH were evaluated. Results: The results of the present study on 63 patients (70% male; mean age, 67.02 years) showed a significant positive correlation between the MPAD and NT-proBNP level (r = 0.444, P < 0.001). Moreover, a significant positive relationship was observed between the pulmonary artery pressure (PAP) and NT-proBNP (r = 0.353, P = 0.005) and also between MPAD and PAP (r = 0.306, P = 0.015). In PAH patients, the mean values of MPAD, PAP, and NT-proBNP were 32.58 mm, 47.9 mmHg, and 6563 pg/mL, respectively. Conclusion: Considering the significant positive correlation between PAP, MPAD, and NT-proBNP level in subgroup comparisons based on MPAD and PAP, if the MPAD is abnormal on CT scan, additional echocardiographic assessments and serum NT-proBNP measurements can be helpful.
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