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Equine Vet J. 2020 Jan 31. doi: 10.1111/evj.13244. [Epub ahead of print]

Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine.

Author information

1
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
2
K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.

Abstract

BACKGROUND:

Clodronate is a non-nitrogenated bisphosphonate approved for use in horses. There are no peer reviewed published reports describing the pharmacokinetics or evaluating renal health indices and urinary excretion patterns in conjunction with plasma and synovial fluid concentration following the systemic administration of clodronate to horses.

OBJECTIVES:

Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses.

STUDY DESIGN:

Experimental study with repeated measures.

METHODS:

Six healthy adult horses received a single intramuscular dose of clodronate (1.8 mg/kg). Blood, synovial fluid and urine were collected prior to and after administration of clodronate up to 72, 48 and 168 hours respectively. Drug concentrations were measured using LC-MS/MS and non-compartmental pharmacokinetic analysis was performed. Renal function indices were also evaluated.

RESULTS:

Clodronate was quantifiable for up to 24 hours in plasma and 48 hours in synovial fluid and detected at all time points in urine. Maximum plasma concentration of clodronate 210±68.2 ng/mL occurred at approximately 34.8±0.2 minutes after administration, while peak synovial concentration (57.7±32.8 ng/mL) occurred at 2.67±2.32 hours after administration and peak urine concentration (88,358.2±79,521.4 ng/mL) occurred at 2.67±2.58 hours post administration. Terminal half-life in plasma was 3.32±1.25 hours and was 4.8±3.05 hours in synovial fluid. Creatinine concentrations rose significantly after treatment but remained within normal adult reference ranges at all times.

MAIN LIMITATIONS:

Limited number of animals and sampling times and absence of urine collection for determination of concentration beyond 7 days.

CONCLUSIONS:

Clodronate is rapidly cleared from the blood and synovial fluid. It has variable and biphasic urinary excretion. While significant increase in blood creatinine concentrations were present after a single intramuscular dose of clodronate, values were never above the normal reference range. Further studies are warranted in horses undergoing exercise and those undergoing multiple dosing schemes.

KEYWORDS:

Osphos; bisphosphonate; clodronate disodium; horse; pharmacokinetics

PMID:
32003488
DOI:
10.1111/evj.13244

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