Category Archives: aminoglycosides

Cockcroft-Gault equation remains an effective way to estimate GFR

aminoglycosides, Pharmacokinetics, ,

From The Annals of Pharmacotherapy Vol. 44, No. 6, pp. 1030-1037:

Evaluation of Aminoglycoside Clearance Using the Modification of Diet in Renal Disease Equation Versus the Cockcroft-Gault Equation as a Marker of Glomerular Filtration Rate

BACKGROUND: Accurate estimation of kidney function is essential for safe administration of renally cleared drugs. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault (CG) equation as an estimation of glomerular filtration rate. Few data exist regarding the utility of the Modification of Diet in Renal Disease (MDRD) equation in drug dosing.

OBJECTIVE: To evaluate glomerular filtration rate based on creatinine clearance (CrCl) derived from the MDRD or the CG equation compared with patient-specific CrCl calculated from aminoglycoside peak and trough concentrations.

METHODS: Medical records of patients who received aminoglycoside antibiotics were reviewed over 1 year. Patients who received aminoglycosides via conventional dosing with peak and trough concentrations at steady state were included. Calculations based on standard pharmacokinetic equations were used to estimate CrCl from aminoglycoside serum concentrations. Patient-specific CrCl estimated from aminoglycoside concentrations was compared with estimated CrCl from the CG or MDRD equation.

RESULTS: Fifty-five patients were included in the final analysis. The primary outcome showed concordance between estimated and actual aminoglycoside clearance was 0.53 (95% CI 0.18 to 0.88) for the CG equation and 0.41 (95% CI 0.04 to 0.78) for the MDRD equation. Subgroup analysis also favored CG as a better predictor of CrCl. This signified a stronger correlation between the CG equation and aminoglycoside clearance.

CONCLUSIONS: Compared with the MDRD equation, the CG equation provided better correlation of estimated glomerular filtration rate for aminoglycoside antibiotics. Institutions should continue to use the CG equation as the standard of practice to safely adjust aminoglycoside doses in patients with renal dysfunction.

It appears that the Cockcroft-Gault (CG) equation remains an effective way to estimate GFR for aminoglycoside PK calculations. I’ve been using the CG equation since my pharmacy school days and have no immediate plans to make a change.

Evaluation of once-daily gentamicin dosing in children with febrile neutropenia

aminoglycosides, cancer, gentamicin, neutropenia, once-daily dosing, pediatrics, Pharmacokinetics

Once-Daily Gentamicin Dosing in Children with Febrile Neutropenia Resulting from Antineoplastic Therapy

Miriam Inparajah, B.Sc.Phm. | Cecile Wong, B.Sc.Phm. | Cathryn Sibbald, B.Sc.Phm. | Sabrina Boodhan, B.Sc.Phm. | Eshetu G. Atenafu, M.Sc. | Ahmed Naqvi, M.B.B.S., MCPS, MRCP | L. Lee Dupuis, M.Sc.Phm., FCSHP

Pharmacotherapy. 2010 Jan;30(1):43-51

Abstract

Study Objectives. To evaluate an existing once-daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose.

Design. Pharmacokinetic analysis of data froma retrospective medical record review.

Setting. Hematology-oncology unit of a university-affiliated pediatric hospital in Canada.

Patients. One hundred eleven patients aged 1–18 years who received once-daily gentamicin between April 2006 and January 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose.

Measurements and Main Results. Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30-minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first-order, one-compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (Cmax) values below the target range (20–25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a Cmax of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioningmethod was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once-daily gentamicin in the following doses achieved a Cmax within or above target in 73% of patients: 1 year to 6 years, 10.5mg/kg/dose; girls ≥ 6 years, 9.5mg/kg/dose; and boys ≥ 6 years, 7.5mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125%ormore of ideal body weight.

Conclusion. The initial gentamicin dosing guidelines were not effective in achieving Cmax. The new proposed dosing guidelines are predicted to achieve a Cmax within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.