Gentamicin pharmacokinetics in old age and frailty


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Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTGentamicin pharmacokinetics show wide inter-individual variability across all age groups and impaired gentamicin clearance is associated with impaired creatinine clearance in older people.Changes in body composition and renal function with old age and frailty are likely to affect the pharmacokinetics of gentamicin.There is current debate on whether the Modification of Diet in Renal Disease (MDRD) equation estimate of glomerular filtration rate (GFR) should replace the Cockcroft Gault equation estimate of creatinine clearance for calculation of doses of renally excreted drugs.WHAT THIS STUDY ADDSThe volume of distribution of gentamicin is not significantly lower in frail than in non frail older people.The correlation between volume of distribution of gentamicin and actual bodyweight is poor in frail and moderate in non frail older people.Gentamicin clearance is significantly lower in frail than in non frail older people.The Cockcroft Gault calculation of creatinine clearance, calculated using ideal bodyweight, gave the best estimate of gentamicin clearance in this population of frail and non frail older people.The MDRD estimate of GFR and Cockcroft Gault estimate of creatinine clearance, calculated using actual bodyweight, overestimate gentamicin clearance in frail and non frail older people.AIMSFrailty, 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.METHODSThis was an observational study of gentamicin pharmacokinetics in a cohort of Australian hospital inpatients aged ≥65 years, who were administered prophylactic intravenous gentamicin.RESULTSOf 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).CONCLUSIONSFrail 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.

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