The administration of drugs to patients suffering from renal impairment can often be problematic, since the drug elimination process can be impaired, with potentially severe results for the patient's health and for the therapy success. Subjects with total renal failure undergoing hemodialysis are obviously more problematic, since the practice itself can have a different impact on different drugs: some of them can be eliminated almost completely through the dialysis membrane, others can be totally retained in the blood. In order to personalize the therapy and adjust the dose, it is necessary to carry out preliminary studies for the determination of drug plasma levels before entering ("arterial blood") and after exiting ("venous blood") the dialysis machine, and also before and after the hemodialysis practice. This peculiar "therapeutic drug monitoring" allows the adjustment of the administered dose according to the possible different elimination rate, thus avoiding both over- and under- doses. The determination of the drug "dializability" is particularly important for compounds having a narrow therapeutic window, such as opioids and related substances used for pain management in oncology and in other contexts. Of course, all active metabolites an their dializability should also be taken into account, to avoid any underestimation of the total pharmacological effect. Aim of this research is thus the development of analytical approaches that can be used for the study of the dializability of opioid drugs used for pain management in patients undergoing hemodialysis, focusing in particular on oxycodone, one of the most widely used drug for this purpose, together with the two active metabolites noroxycodone and oxymorphone. Two methods have been developed and compared, one based on UHPLC with DAD detection and one based on LC coupled to tandem mass spectrometry (MS/MS). The pre-treatment of plasma samples includes a solid phase extraction (SPE) procedure on a reversed phase sorbent. Preliminary results are promising in terms of extraction yields and sensitivity for the three analytes. The methods are currently undergoing validation and the study will continue with the analysis of plasma samples from several patients, drawn before and after subjecting them to hemodialysis.

Analytical approaches for the monitoring of hemodialysis patients undergoing oxycodone therapy

MANDRIOLI, ROBERTO;SAMOLSKY DEKEL, BOAZ GEDALIAHU;RAGGI, MARIA AUGUSTA
2013

Abstract

The administration of drugs to patients suffering from renal impairment can often be problematic, since the drug elimination process can be impaired, with potentially severe results for the patient's health and for the therapy success. Subjects with total renal failure undergoing hemodialysis are obviously more problematic, since the practice itself can have a different impact on different drugs: some of them can be eliminated almost completely through the dialysis membrane, others can be totally retained in the blood. In order to personalize the therapy and adjust the dose, it is necessary to carry out preliminary studies for the determination of drug plasma levels before entering ("arterial blood") and after exiting ("venous blood") the dialysis machine, and also before and after the hemodialysis practice. This peculiar "therapeutic drug monitoring" allows the adjustment of the administered dose according to the possible different elimination rate, thus avoiding both over- and under- doses. The determination of the drug "dializability" is particularly important for compounds having a narrow therapeutic window, such as opioids and related substances used for pain management in oncology and in other contexts. Of course, all active metabolites an their dializability should also be taken into account, to avoid any underestimation of the total pharmacological effect. Aim of this research is thus the development of analytical approaches that can be used for the study of the dializability of opioid drugs used for pain management in patients undergoing hemodialysis, focusing in particular on oxycodone, one of the most widely used drug for this purpose, together with the two active metabolites noroxycodone and oxymorphone. Two methods have been developed and compared, one based on UHPLC with DAD detection and one based on LC coupled to tandem mass spectrometry (MS/MS). The pre-treatment of plasma samples includes a solid phase extraction (SPE) procedure on a reversed phase sorbent. Preliminary results are promising in terms of extraction yields and sensitivity for the three analytes. The methods are currently undergoing validation and the study will continue with the analysis of plasma samples from several patients, drawn before and after subjecting them to hemodialysis.
2013
Proceedings of NMMC 2013 - XXII National Meeting on Medicinal Chemistry
S.AT.13
S.AT.13
Roberto Mandrioli; Laura Mercolini; Michele Protti; Boaz Gedaliahu Samolsky Dekel; Maria Augusta Raggi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/187749
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