title: The effect on luteolysis by intensive oral administration of flunixin granules in heifers.
abstract: The objective of the study was to investigate whether oral administration of flunixin meglumine (FM) in the form of granules could prolong the functional life of the corpus luteum in heifers. Previous studies have shown that intensive, i.e. four times daily parental administration of FM can postpone luteolysis. Twelve heifers received an oral dose of 2.2 mg flunixin per kg body weight. Three dosing regimes were used; twice (n = 2), thrice (n = 4) and four times daily (n = 6). The 9-day-treatment period started on Day 14/15 of the oestrous cycle. Blood samples were collected twice daily during the entire experimental period. Frequent samples were withdrawn from Day 14/15 for 10 and 15 days in the control and treatment oestrous cycles, respectively, at 0600, 0800, 1000, 1200, 1400, 1600, 1800 and at 2000 h. The plasma was analysed for the content of the main metabolite of PGF2 alpha, i.e. 15-ketodihydro-PGF2 alpha, and progesterone. A control cycle preceded the treatment cycle so that each heifer acted as its own control. The length of the oestrous cycle was significantly increased when FM was administered thrice, from 18-22 days to 20-24 days (P < 0.05), and four times daily, from 18-21 days to 25-27 days (P < 0.01), but not in the twice daily dosing regime (one-way ANOVA). When FM was administered twice and thrice, luteolysis occurred during treatment. However, when the four times daily regime was used, luteolysis was obtained when the treatment had terminated. No changes in progesterone levels were recorded, although the luteal phase increased when the oestrous cycle length was prolonged. The number of PG-pulses decreased significantly, from 6-12 pulses to 0-3 pulses (P < 0.01), when FM was administered four times daily. A reduction was also observed when heifers received the drug thrice, but the decrease was not significant. The oral route of administration was found to be as effective as the parental one to affect the mechanism responsible for luteolysis in heifers. However, to inhibit and postpone luteolysis, administration of FM four times daily is a necessity. Our results show that oral administration of FM in the bovine species can be of value both in research as well as in the clinic, e.g. to support the luteal function.
authors.affiliation: Department of Obstetrics and Gynaecology, Swedish University of Agricultural Sciences, Uppsala, Sweden. kristina.odensvik@mailbox.swipnet.se
authors.forename: K
authors.initials: K
authors.lastname: Odensvik
authors.forename: H
authors.initials: H
authors.lastname: Gustafsson
authors.forename: H
authors.initials: H
authors.lastname: Kindahl
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle / Q000502:physiology*; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects* / Q000502:physiology; D015237:Dinoprost / Q000097:blood; D005260:Female; D007700:Kinetics; D011374:Progesterone / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011374:Progesterone; C014558:flunixin meglumine; D015237:Dinoprost; D003002:Clonixin