Population Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty
Shu Jin Tan, Matthew Cockcroft, Madhu Page‐Sharp, Glenn Arendts, Timothy M. E. Davis, Brioni R. Moore, Kevin T. Batty, Sam Salman, Laurens Manning
Abstract
Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.