Plasma, urine, and synovial fluid disposition of methylprednisolone acetate and isoflupredone acetate after intra-articular administration in horses.
OBJECTIVE--To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylprednisolone acetate (MPA) and isoflupredone acetate (IPA). DESIGN--Descriptive investigation. SAMPLE POPULATION--100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically normal female horses. PROCEDURE--Blood samples were collected at time 0 (before) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after administration of the designated steroid. Complete urine collection for measurement 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 time 0 and 8, 24, 48, 240, and 672 hours after administration of the designated 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, using HPLC with a lower limit of quantification (10 ng/ml). RESULTS--Between 2 and 12 hours after administration, plasma contained < 10 ng of MPA 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, respectively. Synovial fluid from the contralateral joint contained no detectable 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 synovial 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.
Lillich
J D
JD
Department of Veterinary Clinical Sciences, Ohio State University, Columbus 43210, USA.
Bertone
A L
AL
Schmall
L M
LM
Ruggles
A J
AJ
Sams
R A
RA
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D005477:Fluprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006736:Horses / Q000378:metabolism*; D007270:Injections, Intra-Articular / Q000662:veterinary; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D000077555:Methylprednisolone Acetate; D011897:Random Allocation; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
D005938:Glucocorticoids; D000077555:Methylprednisolone Acetate; C065592:isoflupredone acetate; D005477:Fluprednisolone; D008775:Methylprednisolone