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.     

Naproxen in the horse: Pharmacokinetics and side effects in the elderly

It is well-known that old animals show physiologic and/or pathologic variation that could modify the pharmacokinetics of drugs and the related pharmacodynamic response. In order to define the most appropriate therapeutic protocol in old horses, pharmacokinetic profile and safety of naproxen were investigated in horses aged over 18 years after oral administration for 5 days at the dose of 10 mg/kg b.w./day. After the first administration, the maximum concentration (C_max 44.21 ± 9.21 μg/mL) was reached at 2.5 ± 0.58 h post-treatment, the harmonic mean terminal half-life was 6.96 ± 1.73 h, AUC_0–24h was 459.71 ± 69.95 h μg/mL, MRT was 7.44 ± 0.74 h and protein binding was 98.47 ± 2.72%. No drug accumulation occurred with repeated administrations. No clinical and laboratory changes were detected after administration of naproxen. Gastric endoscopies performed after the treatment did not show pathological changes of the gastric mucosa.