Pharmacokinetic and pharmacodynamic correlation in drug therapy
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Answer:
⚫Pharmacokinetics was used to develop dosing regimens for achieving therapeutic drug concentrations for optimal safety and efficacy. ...
⚫The term pharmacodynamics refers to the relationship between drug concentrations at the site of action (receptor) and pharmacologic response.
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Abstract
The relationships between pharmacokinetic (PK)/pharmacodynamic (PD) indices and outcomes were investigated in patients with skin and soft tissue infection (SSTI) who received daptomycin at 4 mg/kg/day. Efficacy was evaluated in 55 patients from whom Staphylococcus aureus was isolated, with success rates of 94.5% and 69.1% for clinical and microbiological responses, respectively. The odds ratio for the relationship between the area under the day 1 concentration-time curve (AUC0-24h) to the MIC and the probability of clinical success was 1.03 (95% confidence interval [CI] 0.73-1.45), and that for the relationship for probability of microbiological success was 0.94 (95% CI 0.81-1.09). In 82 patients in the safety analysis, only 1 met the creatine phosphokinase (CPK) elevation criteria, and this patient's minimum concentration (C(min)) of plasma daptomycin was 5.37 μg/mL. No significant relationship was found between peak CPK and C(min) (Pearson's correlation coefficient -0.0452). In conclusion, no clear correlation between PK/PD indices and the probability of efficacy or safety events was demonstrated when daptomycin was administered in SSTI patients using the clinically recommended dosage of 4 mg/kg/day.