The COX inhibitors indomethacin and meloxicam exhibit anti-emetic activity against cisplatin-induced emesis in piglets

We analysed the effects of four cyclooxygenases (COX) inhibitors on cisplatin-induced emesis in piglets. Ninety-five animals receiving cisplatin (5.5 mg kg(-1), i.v.) were observed for 60 h. One hour prior to cisplatin, controls (n=29) were dosed with a saline solution while experimental animals received an i.v. or i.p. injection of one of the COX inhibitors. Additional injections of COX inhibitor were given at 15 and 39 h after cisplatin administration (or every 6 h in one group receiving diclofenac). The latencies to the first emetic episode (EE) compared to controls (2.1+/-0.4 h) increased in groups receiving naproxen (4.66+/-0.94 h, n=9, 30 mg kg(-1)) and indomethacin (6.19+/-1.13 h, n=7, 10 mg kg(-1)) i.v. Indomethacin significantly decreased the incidence of both the acute (by 40%) and delayed (by 66%) phases of emesis. The total number of EE during the 60 h compared to controls (28.3+/-1.9 EE) was significantly reduced in piglets receiving indomethacin (14.9+/-3.2 EE, n=7) and meloxicam (17.6+/-3.6 EE, n=11, 0.3 mg kg(-1)). Four piglets receiving meloxicam (0.3 mg kg(-1), i.v.) did not vomit during the delayed phase. The anti-emetic activity of two COX inhibitors suggests that prostaglandins contribute to the activation of the emetic reflex in response to cisplatin. (C) 2002 Elsevier Science Ltd. All rights reserved.