Gentamicin pharmacokinetics in old age and frailty

Frailty, a syndrome of decreased physiological reserve that is prevalent in old age, impacts on clinical pharmacology. The aims of the study were to (1) determine whether frailty affects the pharmacokinetics of gentamicin and (2) assess the accuracy of different estimates of body size and renal clearance as estimates of gentamicin pharmacokinetics in older inpatients.

This was an observational study of gentamicin pharmacokinetics in a cohort of Australian hospital inpatients aged ≥65 years, who were administered prophylactic intravenous gentamicin.

Of the 31 participants, 14 were frail and 17 non frail on the Reported Edmonton Frail Scale. The mean volume of distribution of gentamicin was 14.8 ± 1.4 l in frail participants and 15.3 ± 2.2 l in non frail (NS). Volume of distribution correlated best with lean bodyweight. Gentamicin clearance was significantly lower in frail participants (46.6 ± 10.7 ml min(-1)) than in non frail (58.2 ± 12.4 ml min(-1), P=0.01). The Cockcroft Gault estimate of creatinine clearance calculated using ideal bodyweight gave the best estimate of gentamicin clearance (mean error -0.15 ml min(-1), 95% CI -2.67, 2.39). The Cockcroft Gault creatinine clearance calculated using actual bodyweight and the estimated glomerular filtration rate from the modified diet in renal disease equation overestimated gentamicin clearance, with mean errors of -10.15 ml min(-1) (95%CI -13.60, -6.71) and -18.86 ml min(-1) (95% CI -22.45, -15.27), respectively. The Cockcroft Gault creatinine clearance calculated using lean bodyweight underestimated gentamicin clearance (mean error 6.54 ml min(-1), 95% CI 4.18, 8.90).

Frail older people have significantly lower gentamicin clearance than non frail. The best estimate of gentamicin clearance is obtained from the Cockcroft Gault creatinine clearance calculated using ideal bodyweight.