Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats

Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.     

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.     

Ex vivo investigation of the use of hydrothermal energy to induce chondrocyte necrosis in articular cartilage of the metacarpophalangeal and metatarsophalangeal joints of horses

OBJECTIVE: To evaluate the use of hydrothermal ablation of articular cartilage for arthrodesis in horses through investigation of the effects of joint lavage with physiologic saline (0.9% NaCI) solution (80 degrees C) for various treatment times on chondrocyte viability in the articular cartilage of the metacarpophalangeal and metatarsophalangeal joints of cadaveric horse limbs. Sample Population-7 pairs of metacarpophalangeal and 8 pairs of metatarsophalangeal joints from 8 Thoroughbreds. PROCEDURE: The horses were euthanatized for reasons unrelated to musculoskeletal disease. On a random basis, 1 joint of each pair underwent intra-articular lavage for 5, 10, or 15 minutes with heated saline solution (80 degrees C); the other joint underwent sham treatment of similar duration with saline solution at 22 degrees C (control). Cartilage samples from the distal articular surface of metacarpus III (or metatarsus III), the proximal surface of the proximal phalanx, and the lateral and medial proximal sesamoid bones were assessed for chondrocyte viability via confocal microscopy and viability staining following enzymatic digestion. RESULTS: Compared with the control joints, findings of both viability assays indicated that the percentage of sites containing viable chondrocytes in heat-treated joints was decreased.Treatment hazard ratios of 0.048 (confocal microscopy) and 0.2 (digestion assay) were estimated. Histologically, periarticular soft tissues had minimal detrimental effects after heat treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Ex vivo intra-articular lavage with saline solution at 80 degrees C resulted in the death of almost all articular chondrocytes in the joint. This technique may be a satisfactory method for extensive cartilage ablation when performing arthrodesis by minimally invasive techniques.     

Assessing the role of federal community assistance programs to develop biomass utilization capacity in the western United States

As forest biomass utilization becomes cost effective to harvest, more areas at risk of catastrophic wildfire can be thinned of dense brush and small diameter trees. In an effort to increase biomass utilization, the USDA Forest Service granted more than $36 million in National Fire Plan-Economic Action Program funds in the western United States during fiscal years 2001 to 2003. Interviews with program coordinators and grant recipients were used to characterize the types of investment strategies used and to assess accomplishments relative to national fuels reduction objectives. Findings include a strong emphasis on grants leveraging other funding sources, coordination of resources to increase utilization capacity, and the need for technical assistance to facilitate project design and implementation. We conclude that community assistance programs may help to create the type of utilization capacity necessary to reduce hazardous fuels, but that sustained progress will depend on synergistic activities on multiple fronts and improved demonstration of program accomplishments.