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PHARMACOKINETICS

Meropenem and Continuous Renal Replacement Therapy: In Vitro Permeability of 2 Continuous Renal Replacement Therapy Membranes and Influence of Patient Renal Function on the Pharmacokinetics in Critically Ill Patients

Arantxazu Isla, MSc, Javier Maynar, MD, José Ángel Sánchez-Izquierdo, PhD, Alicia R. Gascón, PharmD, Alazne Arzuaga, MSc, Esther Corral, MD and José Luis Pedraz, PharmD

From the Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain (Ms Isla, Dr Gascón, Ms Arzuaga, and Dr Pedraz), the Intensive Care Unit, Santiago Apóstol Hospital, Vitoria-Gasteiz, Spain (Drs Maynar and Corral), and the Intensive Care Unit, Doce de Octubre Hospital, Madrid, Spain (Dr Sánchez-Izquierdo).

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 ± 0.12) was similar to the unbound fraction (0.79 ± 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Key Words: Continuous renal replacement therapies • meropenem • pharmacokinetics • critically ill

Address for reprints: Dr José Luis Pedraz Muñoz, Laboratorio de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia. Paseo de la Universidad no 7. 01006 Vitoria-Gasteiz, Spain.


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