JAC Advance Access originally published online on March 16, 2005
Journal of Antimicrobial Chemotherapy 2005 55(5):616-627; doi:10.1093/jac/dki066
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Patient adherence to prescribed antimicrobial drug dosing regimens
1 AARDEX Ltd, Zug, Switzerland; 2 Department of Biostatistics and Medical Informatics, University of Liège, Liège, Belgium, 3 Pharmaco-epidemiology Group, Maastricht University, Maastricht, The Netherlands; 4 Department of Biopharmaceutical Sciences, University of California San Francisco Medical Center, San Francisco, CA, USA
* Correspondence address. AARDEX Ltd, Rue des Cyclistes Frontière 24, B-4600 Visé, Belgium. Tel: +32-4-374-86-35; Fax: +32-4-374-86-22; Email: bernard.vrijens{at}aardex.net
The aim of this article is to review current knowledge about the clinical impact of patients' variable adherence to prescribed anti-infective drug dosing regimens, with the aim of renewing interest and exploration of this important but largely neglected area of therapeutics. Central to the estimation of a patient's adherence to a prescribed drug regimen is a reliably compiled drug dosing history. Electronic monitoring methods have emerged as the virtual ‘gold standard’ for compiling drug dosing histories in ambulatory patients. Reliably compiled drug dosing histories are consistently downwardly skewed, with varying degrees of under-dosing. In particular, the consideration of time intervals between protease inhibitor doses has revealed that ambulatory patients' variable execution of prescribed dosing regimens is a leading source of variance in viral response. Such analyses reveal the need for a new discipline, called pharmionics, which is the study of how ambulatory patients use prescription drugs. Properly analysed, reliable data on the time-course of patients' actual intake of prescription drugs can eliminate a major source of unallocated variance in drug responses, including the non-response that occurs and is easily misinterpreted when a patient's complete non-execution of a prescribed drug regimen is unrecognized clinically. As such, reliable compilation of ambulatory patients' drug dosing histories has the promise of being a key step in reducing unallocated variance in drug response and in improving the informational yield of clinical trials. It is also the basis for sound, measurement-guided steps taken to improve a patient's execution of a prescribed dosing regimen.
Keywords: compliance , directly observed therapy , drug delivery systems , viral load , antiretroviral drugs , pharmacokinetics , pharmacodynamics , pharmacometrics , pharmionics , tuberculosis , human inmunodeficiency virus (HIV) , assay sensitivity
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