PLASMA, URINE, AND SYNOVIAL-FLUID DISPOSITION OF METHYLPREDNISOLONE ACETATE AND ISOFLUPREDONE ACETATE AFTER INTRAARTICULAR ADMINISTRATION IN HORSES

Objective-To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylp rednisolone acetate (MPA) and isoflupredone acetate (IPA). Design-Desc riptive investigation. Sample Population-100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically norma l female horses. Procedure-Blood samples were collected at time 0 (bef ore) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after admini stration of the designated steroid. Complete urine collection for meas urement of designated steroid was accomplished by use of occluding 28- F balloon catheters. Synovial fluid samples were aseptically aspirated from the injected and contralateral uninjected tarsocrural joint at t ime 0 and 8, 24, 48, 240, and 672 hours after administration of the de signated steroid. All samples were screened by ELISA to detect parent drug or metabolite equivalent, with a sensitivity of 2.5 ng/ml for MPA and 0.1 ng/ml for IPA. If drug was detected by ELISA in the plasma or synovial fluid, the samples were further quantified and specified, us ing HPLC with a lower limit of quantification (10 ng/ml). Results-Betw een 2 and 12 hours after administration, plasma contained < 10 ng of M PA or IPA/ml (parent drug or metabolite equivalent), as intermittently detected by ELISA. Parent drug or metabolite equivalent was detected in the urine for 24 and 72 hours after injection of IPA and MPA, respe ctively. Synovial fluid from the contralateral joint contained no dete ctable MPA or IPA at any sample collection time. Median half-life for MPA, as detected by HPLC, was 10.3 hours (range, 6.1 to 10.6) in the s ynovial space. Median half-life for methylprednisolone, as detected by HPLC, was 10.4 (range, 9.9 to 32.1) hours. Conclusions-Both steroids appeared to be rapidly hydrolyzed to their respective ester forms, as detected by HPLC. The ELISA appeared to be a useful screening tool for detection of corticosteroids in this variety of body fluids.