Pharmacokinetics and Effects of Alkalization During Oral and Intravenous Administration of Naproxen in Horses

The use of suitable therapeutic protocols is particularly important when extra-label drugs are used or when physiological parameters are modified, as in the case of the administration of alkaline substances to racehorses. The pharmacokinetics of naproxen (NAP), after both intravenous (iv) and oral administration of 10 mg/kg body weight (BW), was investigated in horses under normal metabolic conditions and in horses whose conditions were modified by the iv administration of 250 mg/kg BW of sodium bicarbonate (NaHCO₃). The hypothesis that blood and consequent urinary alkalization could modify NAP pharmacokinetics was evaluated. Drug quantification was performed on serum and urine using High Performance Liquid Chromatography (HPLC) with ultraviolet-visible detection. Results were also integrated with cycloxygenase (COX)-inhibition published data to suggest an appropriate schedule for NAP dosage in horses. After iv administration, NAP was rapidly distributed (t_1/2α: 0.71 ± 0.43 iv NaHCO₃ and 0.55 ± 0.62 hours No NaHCO₃), whereas its elimination was quite slow (t_1/2β: 6.74 ± 0.41 hours), particularly in iv NaHCO₃ animals (t_1/2β: 8.95 ± 1.37 hours). After oral treatments, NAP was more rapidly absorbed and elimination was slower in iv NaHCO₃ animals (t_1/2λ_z: 17.50 ± 6.66 vs. 7.17 ± 0.91 hours). The oral bioavailability of NAP was approximately 87% and 77% in No NaHCO₃ and iv NaHCO₃, respectively. Urinary excretion of the drug as a parent compound was low. The alkalization procedure did not anticipate the elimination of the acidic drug as expected, but it also influenced the absorption of the drug that was administered orally. The dosage scheme of 10 mg/kg BW iv or orally seems to be appropriate to produce an anti-inflammatory effect for 12 to 24 hours.     

Comparison of Computed Tomographic and Radiographic Popliteal Lymphangiography in Normal Dogs

Objective: To (1) describe computed tomographic (CT) popliteal lymphangiography; (2) compare the number of thoracic duct (TD) branches detected by CT and by radiography after popliteal lymphangiography; and (3) to compare the number of branches detected after left and right popliteal lymphangiography. Study Design: Experimental study. Animals: Adult dogs (n=6). Methods: A randomly selected popliteal lymph node was percutaneously injected with 12 mL iodinated contrast medium through a 25‐g butterfly catheter over 4–5 minutes. Lateral and ventrodorsal (VD) thoracic radiograph projections and thoracic CT were performed. The procedure was repeated using the contralateral lymph node after a 48–72 hours washout period. Results: One dog had TD branches visible on CT but not on radiographs. A significantly greater number of TD branches were observed with CT popliteal lymphangiography compared with lateral and VD radiographic popliteal lymphangiography (P=.003 and P<.001, respectively). The number of visible TD branches observed between the 6th thoracic and 1st lumbar vertebrae were not significantly different in these dogs (P=.146). A significant difference in number of TD branches observed was not found after left or right popliteal lymph node injection (P=.097). Conclusions: CT popliteal lymphangiography consistently identified a greater number of TD branches when compared with radiographic popliteal lymphangiography. Injection of either popliteal lymph node resulted in the same number of TD branches being observed.