Areas of Interest: Palliative Care, Neuropathic and Nociceptive Pain Biomarkers, Clinical Pharmacokinetics-Pharmacodynamics, Population PKPD, Pharmacometrics, Epidemiology, Data Visualization and Analytics, and Clinical Ethics.
Overall Research Goal
To improve clinical outcomes and improve the quality of a patient’s life by combining systems biology with PKPD with an emphasis on clinical endpoints relevant to the patient. The use of quantitative and qualitative research techniques to ensure that patient’s perceive the clinical endpoint as an improvement in their quality of life.
I. Precision Analgesia for Chronic Cancer Pain
Chronic pain in advanced cancer patients often presents as a mixture of nociceptive and neuropathic pain. Although nociceptive pain responds easily to opioid treatment, neuropathic pain may require other treatments or high doses of opioids. However, high dose opioid prescribing remains a diagnostic conundrum for the palliative care clinician since it may reflect disease progression, pain processing changes, opioid-induced hyperalgesia, or non-physical factors affecting pain expression. My research seeks to identify a pain phenotype via pain histories, or through the development of an objective pain biomarker that could aid in the differentiation of nociceptive, neuropathic, and psychogenic factors. Current work is focused on the identification of pain-specific microRNA's using genomic analysis of network perturbations.
II. Precision Opioid Analgesia
Disease states can alter the established PKPD relationships of drugs. Earlier work in end-stage renal disease determined that H3G accumulation is associated with peak pain experience just prior to dialysis. Chronic opioid therapy in advanced cancer patients may result in opioid neurotoxicity characterized by hyperalgesia, CNS-excitation, myoclonus, and acute delirium. The mechanism of this reaction is poorly understood as are contributing factors such as renal dysfunction, concomitant medications which alter normal blood-brain barrier transport. This research is focused on using classical epidemiological techniques to evaluate the effect of concomitant medications on the lethality of opioids and to use sparse sampling population PKPD techniques to evaluate concentration-effect relationships in this patient population.
III. Biomarkers for Immunotherapy in Solid Organ Transplantation
Therapeutic drug monitoring of immunosuppressive drugs for solid organ transplantation remains problematic due to high variability combined with poor sensitivity and specificity of drug concentrations. Biomarkers offer the potential to reveal drug activity after the expression of PK and PD variability. Genomic based biomarkers offer the potential to improve dosing of immunosuppressive drugs in solid organ transplantation.
IV. Meaning of Life and the Palliative Care-Euthanasia Discussion
Meaning of life is increasingly being evaluated and discussed in palliative care patients. With the legalization of medically assisted dying in Canada, it is not clear when patient will choose a palliative care route which provides supportive care designed to improve the quality of existing life or choose a path which hastens death. This research seeks to evaluate meaning of life along with symptom control as an indicator of quality of life. The role of medications in symptom control is well established, but the influence of medications directly on quality of life or meaning of life has not been studied.
Davison, S. N., and P. R. Mayo. "Pain management in chronic kidney disease: the pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients." Journal of Opioid Management 4, no. 6 (2007): 335-6.
Busque, S., M. Cantarovich, S. Mulgaonkar, R. Gaston, A. Osama Gaber, P. R. Mayo, S. Ling, R. B. Huizinga, and H‐U. Meier‐Kriesche. "The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation." American Journal of Transplantation 11, no. 12 (2011): 2675-2684.
Ling, Spencer Y., Robert B. Huizinga, Patrick R. Mayo, Richard Larouche, Derrick G. Freitag, Launa J. Aspeslet, and Robert T. Foster. "Cytochrome P450 3A and P‐glycoprotein drug–drug interactions with voclosporin." British journal of clinical pharmacology 77, no. 6 (2014): 1039-1050.
Mayo, P. R., S. Y. Ling, R. B. Huizinga, D. G. Freitag, L. J. Aspeslet, and R. T. Foster. "Population PKPD of voclosporin in renal allograft patients." The Journal of Clinical Pharmacology 54, no. 5 (2014): 537-545.
Thai, V., Ghosh, S., Tarumi, Y., Wolch, G., Fassbender, K., Lau, F., DeKock, I., Mirosseini, M., Quan, H., Yang, J. and Mayo, P.R., 2016. Clinical prediction survival of advanced cancer patients by palliative care: a multi-site study. International journal of palliative nursing, 22(8), pp.380-387.