The administration of flumethasone, by three different routes, its measurement in the plasma and some effects on wool growth in Merino wethers.
Flumethasone was given to Merino wethers weighing 30-50 kg at rates of 0.62-1.35 mg/kg(0.75) by intravenous (experiments 1 and 2), intraruminal (experiment 4) and subcutaneous (experiment 5) routes over 8 days. In experiment 3, 1.2 mg flumethasone/kg(0.75) was given intravenously over 4, 5 or 6 days. The plasma concentration profiles showed concentrations in the order: intravenous greater than subcutaneous greater than intraruminal. Plasma concentration patterns usually were highest during the first 48 h of infusion followed by relatively stable values. This last feature was not evident in experiments when the rate of hormone infusion was increased. Estimates of the metabolic clearance rates for flumethasone in experiments 1, 2 and 5 were 200-700 ml/min during the equilibrium concentration periods. The effects of flumethasone on some aspects of wool growth revealed interactions between the routes of administration, the period of dosage and the rate of wool growth in the recipients. In experiments 1 and 2 intravenous infusion of 1.20-1.33 mg flumethasone/kg(0.75) caused the shedding of all wool fibres about 30 days after treatment. Some effects of dosing sheep with flumethasone at a time when wool growth was decreasing were also observed in experiment 2. Flumethasone given at a rate of 1.2 mg/kg(0.75) over 4, 5 or 6 days caused the shedding of only some wool fibres which were firmly retained on the sheep by the continuous fibres. Intraruminal and subcutaneous infusions of 0.62-1.35 mg flumethasone/kg(0.75) had similar results to the last in the majority of animals although in a few cases no discontinuity of wool fibres was observed. Recovery in wool growth was observed after treatment. Animals regained their pretreatment wool growth in experiments 1, 4 and 5 by 60 days after treatment and probably equalled at that time wool growth in controls. Recovery was retarded in some individuals in experiment 2 and in some groups in experiment 3. In experiment 1, 21 days wool growth was estimated to have been lost. Some aspects of complete versus partial shedding of wool fibres are discussed particularly with reference to wool harvesting. Some similarities in the appearance of fleeces of steroid-treated sheep and naturally shedding animals are also discussed. In some experiments, particularly when the infusion rate of flumethasone was increased (experiment 3), the sheep showed temporary but significant feed refusals during, but more commonly after, treatment. Speculative discussion as to the metabolic causes of this response is included.
D000818:Animals; D004032:Diet; D005443:Flumethasone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007441:Intubation, Gastrointestinal; D008657:Metabolic Clearance Rate; D012756:Sheep / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014935:Wool / Q000254:growth & development*
D005443:Flumethasone; D006854:Hydrocortisone