Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine.
Osphos
bisphosphonate
clodronate disodium
horse
pharmacokinetics
Journal
Equine veterinary journal
ISSN: 2042-3306
Titre abrégé: Equine Vet J
Pays: United States
ID NLM: 0173320
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
07
05
2019
revised:
26
12
2019
accepted:
12
01
2020
pubmed:
1
2
2020
medline:
6
8
2020
entrez:
1
2
2020
Statut:
ppublish
Résumé
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. Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses. Experimental study with repeated measures. 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 noncompartmental pharmacokinetic analysis was performed. Renal function indices were also evaluated. 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 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. Limited number of animals and sampling times and the absence of urine collection for determination of concentration beyond 7 days. Clodronate is rapidly cleared from the blood and synovial fluid. It has variable and biphasic urinary excretion. While significant increase in blood creatinine concentrations was 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses.
STUDY DESIGN
METHODS
Experimental study with repeated measures.
METHODS
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 noncompartmental pharmacokinetic analysis was performed. Renal function indices were also evaluated.
RESULTS
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 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
CONCLUSIONS
Limited number of animals and sampling times and the absence of urine collection for determination of concentration beyond 7 days.
CONCLUSIONS
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 was 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.
Substances chimiques
Clodronic Acid
0813BZ6866
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
725-732Subventions
Organisme : Louisiana State University Equine Health Studies Program
Informations de copyright
© 2020 EVJ Ltd.
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