Pharmacokinetic studies in old age and frailty: Systematic review of the utilization of population modeling. — The Association Specialists
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Pharmacokinetic studies in old age and frailty: Systematic review of the utilization of population modeling. (422)

Claire F Johnston 1 , Carl MJ Kirkpatrick 2 , Andrew J McLachlan 3 , Sarah N Hilmer 1
  1. Laboratory of Ageing and Pharmacology/Northern Clinical School, Kolling Institute of Medical Research/University of Sydney, Sydney, NSW, Australia
  2. Centre for Medicine Use and Safety, Monash University, Melbourne, VIC, Australia
  3. Centre for Education and Research on Ageing/Faculty of Pharmacy, Concord RG Hospital/University of Sydney, Sydney, NSW, Australia

Introduction. Older adults are major users of medicines who often require dose adjustment due to age- or disease- related physiologic changes, intercurrent disease and multiple medicines.  Understanding and characterizing variability is key to optimal dose selection in older people, especially those who are frail. In population pharmacokinetic (PopPK) analyses the population of patients (rather than individuals) is the unit of analysis and data can be combined from individuals to determine average values and quantitate the relative impact of influential covariates.

Aims. The aim of this review was to investigate the utilization and quality of PopPK studies in people over 65 years of age.

Methods. A systematic search of MEDLINE and PubMed search identified 330 papers using the search term “population pharmacokinetics”. Restrictions set on papers that describe research in were age group over 65 years; articles in English; published 2005-2013 (September); studies conducted in humans; and where full-text was available. 120 papers were excluded because they did not meet these restrictions.

Results. 210 papers were analysed. The median(range) number of patients in the studies was 100(5-3355), with most using NONMEM software for analysis and 86% investigated age as a potential covariate. There were only 21 studies that primarily focused on older people. The commonest drug class investigated was antimicrobials (9/21), most studies used sparse blood sampling methods and patients were generally acutely unwell. Some studies were translated into dosing guidelines specific for older people, although these were generally at a local level. Author affiliations were primarily pharmacology or a specialist area, such as microbiology or anesthetics, with no study coming from a geriatrics or aged care department. No studies were identified on the use of PopPK to determine the impact of an objective measure of frailty on pharmacokinetics in older people. There were only 9 papers found over the last 25 years (using some different search restrictions) that used some measure of frailty to investigate pharmacology in older people

Discussion. The use of PopPK in older people is still limited despite a significant gap in knowledge on optimal dosing for older people, particularly the frail. There is potential for further application in understanding clinical pharmacology in frail older people to optimize medication safety and efficacy.