Abstract
This review summarizes how possible age-related changes in tacrolimus and cyclosporine pharmacokinetics and pharmacodynamics may influence drug dosing and monitoring in the elderly, and highlights how micro-sampling may be useful in this cohort in the future. Advancing biological age leads to physiological changes that can affect drug absorption, distribution, metabolism and excretion, as well as immune system responsiveness. Some studies have shown that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors, suggesting that doses may need to be lowered in elderly recipients. Only one study has examined how aging effects drug target enzyme activity and demonstrated that age does not correlate with the calcineurin inhibitor half-maximal inhibitory concentration. Several studies have shown elderly kidney transplant recipients have increased risk of both morbidity and mortality, compared to younger adults due to increased susceptibility to immunosuppressant side effects, particularly cardiovascular disease, infection and malignancy. Current immunosuppressant dosing and monitoring protocols often make no adjustments for age. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established. Blood draw by micro-sampling may be useful for drug monitoring in this cohort in the future, as blood collection is minimally invasive and less painful than venepuncture. Micro-sampling could also make further pharmacokinetic, pharmacodynamics and outcome studies in the elderly more feasible.
Highlights
Kidney transplantation is first-line treatment for younger patients with end stage renal disease as compared to dialysis, it provides both an increased life expectancy and improved quality of life (Chadban et al, 2012; Dreyer et al, 2015; Registry, 2017; Procurement and Transplantation Network, 2020; Scuderi et al, 2020)
A rise in the prevalence of transplantation in the elderly has been attributed to an aging population (Petzinger et al, 2006), increased use of expanded criteria donor kidneys (Dreyer et al, 2015), and improvements in transplant outcomes (Miura et al, 2009)
This review summarizes how possible age-related changes in calcineurin inhibitor pharmacokinetics and pharmacodynamics may influence drug dosing and monitoring in the elderly, and highlights how micro-sampling may be useful in this cohort in the future
Summary
Kidney transplantation is first-line treatment for younger patients with end stage renal disease as compared to dialysis, it provides both an increased life expectancy and improved quality of life (Chadban et al, 2012; Dreyer et al, 2015; Registry, 2017; Procurement and Transplantation Network, 2020; Scuderi et al, 2020). Renal excretion of drugs is frequently significantly reduced in elderly patients with the glomerular filtration rate declining by approximately 1 ml/ min/1.73 m2 from a person’s 20’s onwards (Staatz and Tett, 2005; Barraclough et al, 2012). It is unclear if biliary excretion and enterohepatic recirculation of drugs is affected by age. Immunosenescence impacts elderly kidney transplant patients by increasing their risk of malignancies, infections, atherosclerosis, autoimmune disorders, and neurodegeneration disorders (Boesmueller et al, 2011; Heinbokel et al, 2013)
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