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 6h 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.
Girod
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Laboratoire de Neurobiologie des Fonctions Végétatives, Département de Physiologie et Neurophysiologie, CNRS FRE 2132 - INRA USC 1147, Faculté des Sciences et Techniques St Jérôme, Université d'Aix-Marseille III, Case 351, 13397 Marseille Cedex 20, France.
Dapzol
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Bouvier
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M
Grélot
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D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D007213:Indomethacin / Q000627:therapeutic use*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D000077239:Meloxicam; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D013552:Swine; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
D000932:Antiemetics; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D002945:Cisplatin; D000077239:Meloxicam; D007213:Indomethacin