Flora Young1, Mary H H Ensom. 1. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Abstract
PURPOSE: The pharmacokinetics of amino-glycosides in patients with chronic spinal cord injury (SCI) is reviewed. SUMMARY: SCI is associated with many physiological changes that can affect disposition of drugs such as aminoglycosides; therefore, dosing of aminoglycosides in this population can be challenging. In general, volume of distribution is significantly higher in the SCI population compared with the non-SCI population; however, clearance and half-life may be larger or no different. When gentamicin is administered intramuscularly, there is no difference in bioavailability when the dose is administered below the level of the injury but absorption appears to be slower in patients with SCI compared with the non-SCI population. Several methods of laboratory assessment of renal function, such as serum creatinine (SCr), 24-hour urine creatinine clearance (CL(cr)), and cystatin C, have advantages and limitations associated with their use in the SCI population. The majority of evidence suggests that SCr and various estimation equations are not accurate methods for assessing renal function in this population. Although measured CL(cr) by 24-hour urine collection is not dependent on muscle mass, wide intrapatient variability in CL(cr) results is still observed. Cystatin C may be a good option in this population; however, its use is limited by its availability. CONCLUSION: Determining appropriate aminoglycoside dosage in patients with SCI is challenging because such patients exhibit physiological changes that lead to their having different aminoglycoside pharmacokinetic values than the general population. Monitoring of aminoglycoside concentrations and calculation of patient-specific pharmacokinetic values can help guide dosage in this patient population.
PURPOSE: The pharmacokinetics of amino-glycosides in patients with chronic spinal cord injury (SCI) is reviewed. SUMMARY: SCI is associated with many physiological changes that can affect disposition of drugs such as aminoglycosides; therefore, dosing of aminoglycosides in this population can be challenging. In general, volume of distribution is significantly higher in the SCI population compared with the non-SCI population; however, clearance and half-life may be larger or no different. When gentamicin is administered intramuscularly, there is no difference in bioavailability when the dose is administered below the level of the injury but absorption appears to be slower in patients with SCI compared with the non-SCI population. Several methods of laboratory assessment of renal function, such as serum creatinine (SCr), 24-hour urine creatinine clearance (CL(cr)), and cystatin C, have advantages and limitations associated with their use in the SCI population. The majority of evidence suggests that SCr and various estimation equations are not accurate methods for assessing renal function in this population. Although measured CL(cr) by 24-hour urine collection is not dependent on muscle mass, wide intrapatient variability in CL(cr) results is still observed. Cystatin C may be a good option in this population; however, its use is limited by its availability. CONCLUSION: Determining appropriate aminoglycoside dosage in patients with SCI is challenging because such patients exhibit physiological changes that lead to their having different aminoglycoside pharmacokinetic values than the general population. Monitoring of aminoglycoside concentrations and calculation of patient-specific pharmacokinetic values can help guide dosage in this patient population.
Authors: Ashley Nguyen; Diana S-L Chow; Lei Wu; Yang Angela Teng; Mahua Sarkar; Elizabeth G Toups; James S Harrop; Karl M Schmitt; Michele M Johnson; James D Guest; Bizhan Aarabi; Christopher I Shaffrey; Maxwell Boakye; Ralph F Frankowski; Michael G Fehlings; Robert G Grossman Journal: J Clin Pharmacol Date: 2021-07-09 Impact factor: 3.126