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A tolerability andpharmacokinetic study of a newinjectable formulation of disodium clodronate in healthyfemale volunteers

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Summary

Disodium clodronate (dichloromethylene bisphosphonic acid, disodium salt; CAS 22560-50-5) is a bisphosphonate that has demonstrated efficacy in patients with a variety of diseases of enhanced bone resorption. Intramuscular clodronate can determine pain at the injection site, it is therefore particularly useful to co-administer a local anaesthetic with clodronate to reduce pain at the injection site. The tolerability and pharmacokinetic of a new formulation of 100 mg disodium clodronate containing 1% lidocaine (test formulation, ChiesiFarmaceutici S.p.A) were investigated incomparisonto the same formulation without thelocal anaesthetic (Clody®) and a marketed formulation containing1% benzyl alcohol (Clasteon®). Thirty healthy female volunteers were treated according to a single dose,double-blind, randomised, three-way cross-over design. The local tolerability was investigated by assessing reddening and hardening at the injection site, and plasma CPK levels. Pain intensity was investigated on the VAS (visual analogue scale) and on the VRS (verbal rating score). Urinary clodronic acid concentrations were determined using a validated specific GC/MS/NCI assay. The statistical analysis on pain assessment showed a significant reduction of pain intensity immediately and up to 2 hours after administration of the new formulation compared to the marketed ones. CPK levels and occurrence of hardening at the injection site did not show statistically significant differences between formulations. No local redness was reported. Clodronate urinary excretion during the 48 h collection interval was not statistically different among the formulations and the 95% confidence intervals were inside the bioequivalence acceptance region, demonstrating comparable bioavailability. It was concluded that the investigated new formulation of 100 mg disodium clodronate was better tolerated than the reference marketed formulations.

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Authors and Affiliations

  1. Pharmacokinetics Department, Chiesi Farmaceutici S.p.A., Via Palermo, 26/A 43100, Parma, Italy

    Gianluigi Poli, Fabrizia Mariotti & Daniela Acerbi

  2. Phase I Unit, Cross Research s.a., Arzo, Switzerland

    Mario Ermanno Corrado

Authors
  1. Gianluigi Poli
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  2. Fabrizia Mariotti
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  3. Mario Ermanno Corrado
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  4. Daniela Acerbi
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Poli, G., Mariotti, F., Corrado, M.E. et al. A tolerability andpharmacokinetic study of a newinjectable formulation of disodium clodronate in healthyfemale volunteers. European Journal of Drug Metabolism and Pharmacokinetics 29, 145–152 (2004). https://doi.org/10.1007/BF03190589

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  • DOI: https://doi.org/10.1007/BF03190589

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