Ciprofloxacin dosing assessment in critically ill elderly patients based on pharmacokinetic- pharmacodynamic analysis by Monte Carlo simulations

Abstract

Infectious disease is a major cause of illness and death in the elderly patients. Antibiotic therapy in these patients is a major challenge for clinicians due to age-related changes such as chronic diseases and poly pharmacy. The recommended dose to achieve favorable pharmacokinetics is 400mg, IV every 12 h and 400mg daily in elderly patients and elderly patients with renal failure respectively. However, failure to achieve a therapeutic concentration in patients admitted in intensive care units and especially in elderly patients is more common. Objective. The objective of this study is to obtain the correlation between creatinine clearance and total clearance of ciprofloxacin to administrate appropriate dose which results in appropriate therapeutic target (AUC/ MIC≥ 250). Material and Methods. The area under ciprofloxacin concentration-time curve in 37 old critically ill patients admitted to the ICU were calculated data analysis through monolix software was performed, to obtain pharmacokinetic data in the studied population. PTA calculated in AUIC≥125 and AUIC≥250 for both group. The pharmacokinetic data of the studied population by Monte Carlo was simulated to 5,000 patients. Findings. 55% of the elderly patients with renal failure vs 100% of the elderly with normal renal function, 15.67% vs. 51.41%, 0.30% vs. 4.2% and 0% vs. 0.05%, respectively, in the MICs of 0.25, 0.5, 1 and 2 achieved a therapeutic goal of AUIC≥125 and 11.11% of the elderly patients with renal impairment compared with 38.46% of patients with normal renal function and 0% versus 5.3% in the MICs of 0.25 and 0.5 achieved a therapeutic goal of AUIC≥250, respectively. Conclusion. Given that MIC is isolated from patients admitted in ICU, in the elderly with normal renal function, in order to achieve optimal treatment and prevent the onset of resistance, the dosage should be Increase at least 1200 mg daily. In patients with renal failure, a daily dose of 400 mg does not guarantee clinical success; it seems that more doses are needed for better treatment response.