[Population pharmacokinetics of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection]

Abstract

Objective: To analyse population pharmacokinetic (PPK) parameter values of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection.

Methods: Hospitalized in Respiratory Intensive Care Unit (RICU) due to severe lower respiratory tract infection and at high risks of Pseudomonas aeruginosa. 43 consecutive elderly patients received an intravenous infusion of ciprofloxacin at a dose of 200/400 mg every 12/24 h empirically. Plasma samples were drawn from Day 4 and at 1, 2, 3, 4, 6, 8 and 12 h after infusion. The serum concentrations of ciprofloxacin were determined by high-performance liquid chromatography (HPLC). Ciprofloxacin population pharmacokinetic analysis was conducted by the NONMEM 7.3.0 software.

Results: Forty patients aged (78 ± 9) years completed the study. A total of 210 serum concentrations were detected. The mean values of clearance and volume of distribution (V1) were 17.8 L/h and 49.8 L respectively. The serum creatinine level influenced ciprofloxacin according to the equation: Clearance - 17.8 × [1 - 0.001 3 × (serum creatinine - 67)] × e(η1i) × 0.659(n) (at a dose of 200 mg, n - 1, at a dose of 400 mg, n - 0; ηi for inter individual random variation). The values of clearance and V1 were multiplied by 0.659 at a dose of 200 mg. At the doses of 200 and 400 mg, the maximum steady-state concentrations (C(max)) were (4.2 ± 1.1) and (5.3 ± 1.21) mg/L, the minimum steady-state concentrations (C(min)) (1.1 ± 1.1) and (0.8 ± 0.4) mg/L and the area under concentration-time curve measured in steady-state up to 24 h after dosing (AUC(0-24 h)) were (45.5 ± 28.1) and (47.2 ± 11.3) mg · h · L⁻¹ respectively.

Conclusions: The clearance of ciprofloxacin in elderly patients significantly decreases as compared with adult patients. Ciprofloxacin PPK model shows a significant influence of serum creatinine level on ciprofloxacin clearance. A single dose of 400 mg may increase serum drug concentration, but causes no in vivo drug retention.