Effect of protein binding of daptomycin on MIC and antibacterial activity.
Article Details
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Lee BL, Sachdeva M, Chambers HF
Effect of protein binding of daptomycin on MIC and antibacterial activity.
Antimicrob Agents Chemother. 1991 Dec;35(12):2505-8. doi: 10.1128/aac.35.12.2505.
- PubMed ID
- 1667253 [ View in PubMed]
- Abstract
A higher rate of clinical failures in patients treated with daptomycin (2 mg/kg of body weight, given once daily) compared with rates in patients treated with conventional regimens caused early termination of this comparative clinical trial. One explanation for these failures could be that daptomycin is highly protein bound and that the concentration of the unbound active drug is too low for antibacterial activity. To assess this explanation, we studied the binding of daptomycin to proteins by using an ultrafiltration method. pH (7.0 to 7.4), temperature (25 or 37 degrees C), or daily freezing and thawing over 2 months had no effect on binding of daptomycin to proteins. We found that daptomycin was bound to albumin (90%) at 4 g/100 ml. Binding of daptomycin was not concentration dependent (2.5 to 80 micrograms/ml). In human serum samples spiked with daptomycin, average binding was 94% +/- 2.4%. In 6 subjects given an intravenous infusion of daptomycin (3 mg/kg), average binding was 90% +/- 2.1%. Susceptibility studies showed that a concentration in serum 20 times the unbound concentration was needed to equal the MIC of the total drug. These results indicate that daptomycin is highly bound (90 to 94%) to albumin and that clinical failure to daptomycin can in part be explained by the low concentration of the unbound drug.
DrugBank Data that Cites this Article
- Drugs
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Daptomycin Alpha-1-acid glycoprotein 1 Protein Humans NoBinderDetails Daptomycin Serum albumin Protein Humans NoBinderDetails