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Objective—To establish practical doses and administration frequencies of fondaparinux for cats that would approximate human therapeutic peak and trough plasma anti–factor Xa activities for thromboprophylaxis (TP) and thrombosis treatment (TT) protocols.
Animals—6 healthy adult purpose-bred cats.
Procedures—Dosage protocols for TP and TT were selected on the basis of a single compartment pharmacokinetic model incorporating data from humans but modified to account for the higher body weight–normalized cardiac output of cats. Fondaparinux was administered at 0.06 mg/kg, SC, every 12 hours (TP) for 7 days in one session, and 0.20 mg/kg, SC, every 12 hours (TT) for 7 days in another, with a minimum of 1 week separating the sessions. Plasma anti–factor Xa activity was measured before fondaparinux administration (day 1) and at 2 (peak) and 12 (trough) hours after drug administration on days 1 and 7. Platelet aggregation and thromobelastographic (TEG) parameters were also measured 2 hours after drug administration on day 7.
Results—Peak plasma anti–factor Xa activities on day 7 for TP (median, 0.59 mg/L; range, 0.36 to 0.77 mg/L) and TT (median, 1.66 mg/L; range, 1.52 to 2.00 mg/L) protocols were within therapeutic ranges for humans. However, only the TP protocol achieved trough anti–factor Xa activity considered therapeutic in humans (median, 0.19 mg/L; range, 0.00 to 0.37 mg/L) on day 7. There were significant changes in the TEG parameters at peak for the TT protocol, suggesting a hypocoagulable state. No significant changes in platelet aggregation were evident for either protocol.
Conclusions and Clinical Relevance—A fondaparinux dosage of 0.06 or 0.20 mg/kg, SC, every 12 hours, was sufficient to achieve a peak plasma anti–factor Xa activity in cats that has been deemed therapeutic in humans. This study provided preliminary data necessary to perform fondaparinux dose-determination and clinical efficacy studies.
Objective—To investigate the pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or IV infusion of penciclovir.
Procedures—Cats received famciclovir (40 [n = 3] or 90  mg/kg, PO, once) in a balanced crossover-design study; the alternate dose was administered after a ≥ 2-week washout period. After another washout period (≥ 4 weeks), cats received an IV infusion of penciclovir (10 mg/kg delivered over 1 hour). Plasma penciclovir concentrations were analyzed via liquid chromatography-mass spectrometry at fixed time points after drug administration.
Results—Mean ± SD maximum plasma concentration (Cmax) of penciclovir following oral administration of 40 and 90 mg of famciclovir/kg was 1.34 ± 0.33 μg/mL and 1.28 ± 0.42 μg/mL and occurred at 2.8 ± 1.8 hours and 3.0 ± 1.1 hours, respectively; penciclovir elimination half-life was 4.2 ± 0.6 hours and 4.8 ± 1.4 hours, respectively; and penciclovir bioavailability was 12.5 ± 3.0% and 7.0 ± 1.8%, respectively. Following IV infusion of penciclovir (10 mg/kg), mean ± SD penciclovir clearance, volume of distribution, and elimination half-life were 4.3 ± 0.8 mL/min/kg, 0.6 ± 0.1 L/kg, and 1.9 ± 0.4 hours, respectively.
Conclusions and Clinical Relevance—Penciclovir pharmacokinetics following oral administration of famciclovir were nonlinear within the dosage range studied, likely because of saturation of famciclovir metabolism. Oral administration of famciclovir at 40 or 90 mg/kg produced similar Cmax and time to Cmax values. Therefore, the lower dose may have similar antiviral efficacy to that proven for the higher dose.
Objectives—To study the functional and structural responses of the right dorsal colon (RDC) of ponies to phenylbutazone (PBZ) in vitro at a concentration that could be achieved in vivo.
Animals—8 adult ponies.
Procedure—Short circuit current and conductance were measured in mucosa from the RDC. Tissues incubated with and without HCO3 – were exposed to PBZ, bumetanide, or indomethacin. Bidirectional Cl– fluxes were determined. After a baseline flux period, prostaglandin E2 (PGE2) was added to the serosal surfaces and a second flux period followed. Light and transmission electron microscopy were performed.
Results—Baseline short circuit current was diminished significantly by PBZ and indomethacin, and increased significantly after addictions of PGE2. After PGE2 was added, Cl– secretion increased significantly in tissues in HCO3-–-free solutions and solutions with anti-inflammatory drugs, compared with corresponding baseline measurements and with control tissues exposed to PGE2. Bumetanide did not affect baseline short circuit current and Cl– fluxes. The predominant histologic change was apoptosis of surface epithelial cells treated with PBZ and to a lesser extent in those treated with indomethacin.
Conclusions and Clinical Relevance—Prostaglandin- induced Cl– secretion appeared to involve a transporter that might also secrete HCO3 –. Both PBZ and indomethacin altered ion transport in RDC and caused apoptosis; PBZ can damage mucosa through a mechanism that could be important in vivo. The clinically harmful effect of PBZ on equine RDC in vivo could be mediated through its effects on Cl– and HCO3 – secretion. (Am J Vet Res 2002;220:934–941)