A population pharmacokinetic study of ceftriaxone in elderly patients using Cystatin C-based estimates of renal function to account for frailty

Objective: Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies.Methods: A prospective population pharmacokinetic study of ceftriaxone in adults over 65-year-old was undertaken. Dried blood spots collected at baseline, and 0.5, 1, 4, 8 and 24 (pre-dose) hours after administration of 1g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified with 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.Results: Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance significantly improved 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 (AUC). For elderly patients with moderate or severe renal impairment, 48-hourly dosing results in greater trough concentrations and total exposure than patients with normal renal function receiving 24-hourly dosing.Conclusions: Cystatin-C based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.