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Related Experiment Videos

Once-daily dosing in dogs optimizes daptomycin safety.

F B Oleson1, C L Berman, J B Kirkpatrick

  • 1Cubist Pharmaceuticals, Inc., Cambridge, Massachusetts, USA. roleson@cubist.com

Antimicrobial Agents and Chemotherapy
|October 19, 2000
PubMed
Summary

Daptomycin dosing every 24 hours, not every 8 hours, may minimize skeletal muscle effects. This finding suggests once-daily daptomycin administration could be safer for patients.

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Area of Science:

  • Pharmacology
  • Toxicology
  • Antibiotic Research

Background:

  • Daptomycin is a lipopeptide antibiotic effective against Gram-positive bacteria.
  • Daptomycin use is associated with skeletal muscle effects.
  • Optimizing daptomycin dosing is crucial to minimize toxicity.

Purpose of the Study:

  • To compare the skeletal muscle effects of daptomycin administered every 24 hours versus every 8 hours.
  • To guide clinical daptomycin dosing for reduced myotoxicity.

Main Methods:

  • Two studies were conducted in dogs over 20 days.
  • Intravenous daptomycin was administered at different dosing intervals (every 24h vs. every 8h).
  • Skeletal muscle effects were assessed by monitoring serum creatine phosphokinase activity and myopathy incidence.

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Main Results:

  • Skeletal muscle effects were more related to the dosing interval than peak drug concentration or AUC.
  • Higher incidence of myopathy and elevated creatine phosphokinase observed with every 8h dosing compared to every 24h dosing.
  • Doses of 25 mg/kg every 8h showed greater effects than 75 mg/kg every 24h, despite lower Cmax.

Conclusions:

  • Once-daily daptomycin administration appears to minimize skeletal muscle toxicity.
  • A longer dosing interval may allow for repair of subclinical muscle damage.
  • Findings suggest that once-daily daptomycin dosing in humans may reduce the risk of myopathy.