Clinical Pharmacokinetics and Individualisation of Drug Dosage Regimens

The objective of any pharmacological treatment is to achieve maximum therapeutic efficacy with minimum toxicity in each patient. In most cases, drugs are administered at the standard dose described in the drug’s technical information, with occasional dose modifications based on renal or hepatic dysfunction. These adjustments are usually based on general nomograms or algorithms. However, clinical practice shows that the administration of fixed doses to all patients can produce different responses. Thus, following administration of the same drug dose, the desired pharmacological effect with minimum toxicity will be achieved in some patients, whereas in others the desired pharmacological effect will not be observed or toxicity may even be high. This interindividual variability in response is largely due to differences in plasma drug concentrations between patients. In this regard, Pharmacokinetics is the science that studies the evolution of drug concentrations in plasma within the body, making it possible to characterise the absorption, distribution, metabolism and excretion of drugs. This science is applied in clinical practice with the aim of explaining drug behaviour according to the individual characteristics of each patient and the state of their disease.

The dosage regimen of a given drug for each specific situation is determined using Bayesian methodology. Prior information about the drug is obtained from pharmacokinetic and pharmacodynamic models developed or described in the scientific literature. Posterior information is obtained from the demographic, clinical, biochemical and disease-related data of each patient, as well as from the dose administered and the measured plasma drug concentrations. This Bayesian adjustment is carried out using specific software programmes in the field of pharmacometrics, such as NONMEM and Monolix. In addition, the R software programme is used for statistical analysis and graph generation.

Personalised medicine is having an increasing impact on the pharmacological treatment of patients. In this context, Clinical Pharmacokinetics plays a key role within personalised medicine by adjusting drug doses according to the characteristics of each patient. Therefore, this knowledge can be offered for integration into routine clinical practice in both public and private hospitals.

To correctly apply the principles of Clinical Pharmacokinetics in patients, multidisciplinary training in other areas of healthcare is required, including biostatistics, programming and population pharmacokinetics, in addition to Pharmacology itself. Personnel must also be able to solve problems in new clinical settings and deal with the complexity of formulating judgements and making decisions based on the pharmacokinetic and clinical information of each patient. As a result, many public and private hospitals in Spain, as well as in many other countries, do not have personnel trained in this branch of Pharmacology and, therefore, treatment is not optimised in many cases. Even hospitals that are beginning to incorporate this activity into their service portfolio require technical support and expertise to carry out dosage individualisation correctly. In this regard, our group has the necessary multidisciplinary expertise, as well as experience in developing projects of the type being offered.

The knowledge and tools are ready for routine application. Based on the clinical data provided by the healthcare centre, the group carries out individualised dosage regimen adjustment with a high degree of reliability.

• Public and Private Hospitals.
• Pharmaceutical Industry (Pharmacokinetics and Pharmacometrics Departments).
• Biomedical Research Centres.

Amelia Ramón López – Department of Engineering