Modeling the influence of non-adherence on antibiotic efficacy: application to ciprofloxacin.
OBJECTIVE
To evaluate the consequences for antibiotic efficacy of different types of poor adherence to a short-term dosing regimen. Ciprofloxacin was taken as an example.


METHODS
A simulation study on a 2-compartment pharmacokinetic model and parameter estimates taken from the literature was performed. Two empirical efficacy measures as well as a specific pharmacodynamic model of the bacterial kill curve were used. Four patterns of non-adherence were investigated: dosage omission, irregular dosing intervals, delayed dosing and treatment discontinuation.


RESULTS
Errors in timing of doses with a standard deviation less than 2 h had a minor effect on antibiotic efficacy. Dosage omission, in contrast, has a significant influence on the antibacterial effect of ciprofloxacin.


CONCLUSIONS
non-adherence patterns are difficult to measure experimentally, thus, recommended dosing regimens should be sufficiently robust against most of the nonintentional disturbances.
Lansky
P
P
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. lansky@biomed.cas.cz
Sanda
P
P
Weiss
M
M
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D001682:Biological Availability; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D015233:Models, Statistical; D013269:Stochastic Processes; D016312:Treatment Refusal / Q000706:statistics & numerical data*
D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin