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. METHOD: 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.

Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic

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