The Pharmaceutical Journal Vol 267 No 7156 p50
July 14, 2001

Comment

Pharmacokinetics is not a rare art but an essential tool for providing proper care

By Neil Caldwell, John Sexton and Chris Green

Pharmacokinetics specifically addr-esses the process and time for drug absorption, distribution, metabolism and elimination. By applying pharmaco-kinetic principles we aim to individualise the dose of drug, and optimise the outcome achieved in each patient. Its application reduces the chance of under-treatment, inadvertent poisoning and avoids dose rel-ated adverse effects. Quite simply, it is the pharmacy profession’s raison d’être.

The underlying principles of pharmaceutical care stress that everyone is an individual with their own beliefs and values and medicine-related needs. Clinical pharmacokinetics, and dosage individualisation, is therefore a core function of all pharmacists who care for individual patients.

The primary aim of pharmacokinetic input must always be focused on the patient and his or her resultant clinical response. Population-based pharmacokinetics increases the likelihood of achieving an appropriate drug concentration. It does not, however, offer any guarantee. After all, if we could successfully predict the serum concentration of a drug in any patient, no blood concentration monitoring would be necessary. Since all patients are different, it is still necessary to measure drug concentrations to ensure safe and effective therapy.

Some pharmacists use clinical pharmacokinetic principles routinely in their daily practice, but many do not. Teachers of pharmacokinetics at undergraduate and postgraduate levels try to empower their students with a zeal for the application of pharmacokinetics knowledge. However, they are constantly frustrated and amazed by the attitudes of teaching and practising colleagues who suggest that pharmacokinetics, like medical statistics, is one of those esoteric arts that most professionals do not need either to understand or to apply. They suggest that clinical pharmacokinetics is a specialist area that can be practised as an option. Substantial numbers of colleagues freely express, “But we don’t do kinetics in our hospital”, or, “We don’t need to apply pharmacokinetics knowledge here.”

Pharmacists are ideally positioned to review all drug therapy for all patients from a pharmacokinetics perspective. An eminent professor of clinical pharmacology used to regale students with a simple statement of fact: “Drugs do not have correct doses; patients do.” We wholeheartedly concur with this pearl of wisdom.

Pharmacokinetics is not simply about digoxin, theophylline and gentamicin. It concerns all medicines for all patients. It appears incongruous that we would routinely endorse a prescription for a young adult, with a staphylococcal skin infection, for flucloxacillin intravenous injection 1g six-hourly, but would immediately contact any doctor who prescribed flucloxacillin capsules 750mg po qds. Where is the logic? Flucloxacillin has a bioavailability of around 50 to 70 per cent, hence the oral dose equivalent could quite reasonably be 1,500mg qds.

The appropriateness of medicine dosing for patients can be examined from a simple review of standard literature such as the British National Formulary or summaries of product characteristics. “What is the most appropriate dose of metoprolol to commence therapy with in an 82-year-old hypertensive?” This could be an everyday occurrence for many pharmacists who care for patients. It is also, in very simple terms, clinical pharmacokinetics. Most colleagues would recognise the reduced capacity of such a patient to metabolise metoprolol, altered pharmacodynamic response and decreased physiological reserve. As such, initiation of low-dose therapy and close monitoring to achieve the desired clinical outcome, would appear sensible. This is a simple illustration of a review of the drug-related needs of an individual from a pharmacokinetics perspective. It does not always involve complicated equations involving exponential calculations.

More complex cases may need a greater understanding of clinical pharmacokinetic principles to answer questions such as, “What is the appropriate dose of chloramphenicol for staphylococcal sepsis in a sick preterm neonate?” From first principles, with a basic understanding of routes of elimination, post-conceptional age and its influence on drug clearance, salt factors, volume of distribution and intended target concentrations, a pharmacist should be the obvious expert to guide dose individualisation.

Clinical pharmacokinetics takes account of an individual’s unique characteristics, and their influence on ability to absorb, distribute, metabolise and eliminate a drug. It is thus not solely concerned with quantification of renal function. To review prescribed therapy from a pharmacokinetic perspective one does not always need a calculator to work out renal function. This fact appears lost on a number of colleagues, who, at the mere suggestion of pharmacokinetics, start number crunching. For example, calculation of creatinine clearance is only necessary for patients who are treated with drugs which are eliminated primarily by glomerular filtration, or have active metabolites. Practitioners often make incorrect assumptions when calculating creatinine clearance, and may not appreciate the limitations of the standard estimations. Other relevant data, which will inform the pharmacist about the appropriateness, or otherwise, of prescribed drug therapy, should also be considered. Aspects such as delayed gastric transit time due to concurrent opiate consumption, altered distribution volume due to ascites or pleural effusion, or reduced hepatic enzyme function because of decreased hepatocyte oxygenation secondary to congestive cardiac failure, must all be considered in the pharmacokinetic review.

Computer programs are not a prerequisite to deliver pharmacokinetic review. Common sense, however, is vital. A computer-generated dose prediction should always be held up for scrutiny and never accepted without question. Ask the following questions: “Does this make sense? What assumptions have been made? Are they valid for the patient under consideration? Does this appear reasonable?” Pharmacokinetics is a helpful guide for pharmacists who endeavour to provide pharmaceutical care. It does not, however, provide any guarantee.

The best place to deliver pharmacokinetic review is at the patient’s bedside, or in direct consultation with the focus of clinical pharmacokinetic activity, the patient. Only in this situation can the pharmacological effect of medication, and the appropriateness or otherwise of medical intervention be assessed.

As a profession we either believe that everyone is the same until we can prove otherwise, or that everyone is different until we can prove that they are part of a homogenous group. If members of our family were on the receiving end of medical intervention, we would hope that their unique characteristics and autonomy were recognised and acknowledged in the formulation of any treatment plan, including the optimisation of drug doses. It would thus be egalitarian to wish individualisation for all.

Choice of correct medicine is only half the challenge that pharmacists face. Getting the right dose for each individual to achieve the defined, and agreed, therapeutic endpoint, requires pharmacists to apply their broad-based scientific training to each and every patient they encounter.

As a matter of routine, pharmacist involvement with clinical pharmacokinetics should be targeted to use pharmacokinetic principles to determine if a drug dose looks reasonable for an individual and to determine whether further pharmacist involvement is required.

Patients will achieve better outcomes from medicines if drug therapy is targeted to their needs using pharmacokinetic principles. Nobody else will do this for patients. Pharmacists must.

The authors are teacher-practitioner pharmacists in Liverpool