Clinical pharmacokinetics in the 21st century. Does the evidence support definitive outcomes?

Clinical pharmacokinetics emerged as a clinical discipline in the late 1960s and early 1970s. Clinical pharmacokinetic monitoring (CPM) helped many pharmacists to enter the clinical arena, but the focus was more on the pharmacists and tools. With the widespread acceptance of pharmaceutical care and patient-focused pharmacy, we now must take a sobering look at how clinical pharmacokinetics fits into the pharmaceutical care process. The existing literature is laden with articles that evaluate the effect of CPM on surrogate end-points. Many pharmacists have also had personal experiences that attest to the usefulness of CPM. Decreased mortality, decreased length of treatment, decreased length of hospital stay, decreased morbidity, and decreased adverse effects from drug therapy have been examined in an effort to measure and evaluate the impact of CPM on patient outcomes. While many of these studies demonstrated significant positive outcomes, several showed that CPM did not have a significant impact on specific patient outcomes. A few studies even found a negative impact on specific patient outcomes. Ultimately, there is good evidence in only a few specific patient groups to support the benefit of CPM. Despite the limitations of data supporting the routine use of CPM in managing drug therapy in diverse populations, many pharmacists continue to expend considerable time and effort in this activity. We need to define those patients who are most likely to benefit from CPM and incorporate this into our provision of pharmaceutical care, while minimising the time and money spent on CPM that provides no value. In redefining the patients who will benefit from CPM, we need to critically re-evaluate clinical studies on the relationship between drug concentration and response. Similarly, we need to pay special attention to recent studies evaluating the impact of CPM on outcomes in specific subpopulations. In the absence of specific studies demonstrating the value of CPM in particular patients, we propose that a more comprehensive decision-making process be undertaken that culminates in the quintessential question: 'Will the results of the drug assay make a significant difference in the clinical decision-making process and provide more information than sound clinical judgement alone?' We also need to consider opportunities to expand the use of CPM for new drugs and where new evidence suggests benefit. Even when there is strong evidence that CPM is useful in managing therapy in particular patient groups, clinicians need to remember that the therapeutic range is no more than a confidence interval and, therefore, we need to 'treat the patient and not the level'. We need to incorporate the patient-specific and outcome-oriented principles of pharmaceutical care into our CPM, even as we utilise CPM as an essential tool in pharmaceutical care.