UMF TGM: LTMPK Project

This project is attempting to create a test centre for monitoring the plasmatic concentrations for drugs with narrow therapeutic index. The aim of the project is the individualization of the therapeutic strategy for patients from the university clinics of Nephrology and Neurology from The Clinical and Emergency County Hospital Tg-Mures by respecting the ethical rules, the Good Clinical Practice rules and Helsinki Declaration. We also attempt to monitor plasmatic concentrations in high risk patients with pediatric oncology treatment (methotrexate, antracyclines).

International reglementations and guides recommend monitoring of plasmatic concentrations in patients using drugs with narrow therapeutic index (antiepileptic drugs such as valproic acid, lamotrigin, fenitoin, antiinfective drugs like gentamicin, antiasthmatic drugs like teophylline etc). This kind of determinations is almost non-existent in Romania except for determination of some immune-suppressing drugs in patients undergoing transplant (cyclosporine, tacrolimus, sirolimus). Overdosing risk (because of individual variability in case of drugs with narrow therapeutic index or in case of drug association that affect the pharmacokinetic transformation and which cannot be avoided in clinical trials) or subdosing risk (due to excessive prudence and in the end it leads to therapeutic inefficacity) is very high and can be avoided by pharmacotherapy monitoring by pharmacokinetic criteria, a very frequent test in European and North American hospitals. In case of chronic renal disease inadequate administration can cause dose dependent toxicity, because it affects drugs abortion, bioavailability and distribution and it modifies renal clearance (by affecting glomerular filtration rate but tubular secretion and reabsorption). K/DOQI (Kidney Disease Outcomes Quality Initiative) recommends treatment initiation depending on therapeutic response and drug plasmatic concentration. Administration rate in order to obtain plasmatic levels in the therapeutic domain is very difficult for antiepileptic drugs also. That is why clinical guides recommend monitoring plasmatic levels in order to assure a positive impact upon therapeutically act quality.

The main objective of the project is to modernize the Drug Testing Laboratory from Targu-Mures, in order to develop the research infrastructure by acquiring high performance modules (mass spectrometry) for already existing apparatus and new equipments with improved technical caracteristics.

The whole developed technical infrastracture will lately be used for determination of plasmatic concentration in some narrow therapeutic index drugs in patients from the university clinics of Nephrology and Neurology from The Clinical and Emergency County Hospital Tg-Mures. This will be a test center that can lately be extended. Monitoring of plasmatic concentrations and individualized therapy will have a positive impact upon patients’ life quality and in long term will determine a cost decrease in treatment due to sustaining of the science –society dialog.

This pilot center will lead to an extension of the research structures, multiple users (university clinics) that can directly use pharmacotherapy monitoring by the pharmacokinetic criteria. Data exchange will be fulfill with similar clinical units in which monitoring of plasmatic concentrations is current practice (we must mention that in Romania monitoring of plasmatic concentrations is regularly done only for patients with transplant and receiving immunosuppressive therapy).