Influence of sevoflurane anesthesia with mechanical ventilation and fluid-therapy on distribution of subcutaneously administered robenacoxib in dogs

Robenacoxib is a novel nonsteroidal anti-inflammatory drug approved for dogs. The present study aimed to evaluate influences of sevoflurane anesthesia on the distribution of robenacoxib in dogs. Ten healthy beagle dogs (1 to 11 years old, 9.3 to 14.3 kg body weight, 6 males and 4 females) were subcutaneously administered robenacoxib (2 mg/kg) under conscious condition or sevoflurane anesthesia inhaled a 1.3-fold predetermined individual minimum alveolar concentration of sevoflurane at a 28-day interval. The dogs under sevoflurane anesthesia were also mechanically ventilated and received fluid-therapy. On each occasion, serum samples were collected from the dogs before and at 5, 15, 30, 60, 120, 180, and 240 min after the robenacoxib administration. Serum robenacoxib concentration was measured by a liquid chromatography-tandem mass spectrometry. Maximum serum concentration of robenacoxib (C(max)) was 2.2 µg/ml [range: 1.2–4.6] (median [range: minimum-maximum]) and time of C(max) (T(max)) was 90 min [range: 60–120] in the conscious dogs. In the sevoflurane-anesthetized dogs, the C(max) significantly declined (1.3 µg/ml [range: 0.8–1.4], P=0.008) and T(max) was delayed (120 min [range: 120–240], P=0.018) compared with those in the conscious dogs. The serum robenacoxib concentration at 240 min (C(240)) decreased to 0.5 µg/ml [range: 0.2–0.9] in the conscious dogs, while it remained higher in the sevoflurane-anesthetized dogs (1.0 µg/ml [range: 0.3–1.4], P=0.011). In conclusion, the anesthetic procedure with sevoflurane, mechanically ventilated, and received fluid-therapy might affect the pharmacokinetics of subcutaneously administered robenacoxib in dogs.