Immunosuppressant drugs--the role of therapeutic drug monitoring.

Abstract

Individualizing a patient’s drug therapy to obtain theoptimum balance between therapeutic efficacy and theoccurrence of adverse events is the physician’s goal.However, achieving this goal is not always straightforward, being complicated by within and betweenpatientvariabilityinbothpharmacokineticsandpharmaco-dynamics. In the early 1960s new analytical techniquesbecame available allowing the measurement of the lowdrug concentrations seen in biological fluids during drugtreatment. This offered the opportunity to reduce thepharmacokinetic component of variability by controllingdrug therapy using concentrations in the body rather thanby dose alone. This process became known as therapeuticdrug monitoring (TDM) [1].Foradrug tobea suitablecandidatefortherapeutic drugmonitoring it must satisfy the following criteria:-There should be a clear relationship between drugconcentration and effect.The drug should have a narrow therapeutic index; thatis, the difference in the concentrations exerting ther-apeutic benefit and those causing adverse events shouldbe small.There should be considerable between-subject phar-macokinetic variability and therefore a poor relationshipbetween dose and drug concentration/response.The pharmacological response of the drug should bedifficult to assess or to distinguish from adverse events.The immunosuppressive drug cyclosporin satisfies allfour of these criteria and yet despite over 19 years ofclinical use with therapeutic drug monitoring, there is nofirm consensus on the best way to use the drug andmonitoring techniques are still evolving [2]. In addition,the number of available agents for use as immuno-suppressants has more than trebled in recent years and therange of diseases in which these drugs are used has alsowidened [3]. The purpose of this review is to examinethe current strategies in use for the therapeutic drugmonitoring of immunosuppressant drugs [4] and to discusssome of the factors that impinge on the monitoring ofthese drugs.