Pediatric Clinical Pharmacology
The work in my laboratory focuses on understanding the basis for inter-individual variation in drug disposition and response in the pediatric patient population. In particular, my work has focused on factors affecting the response to disease-modifying anti-rheumatic drugs (DMARDs), which are commonly used in the treatment of various pediatric autoimmune diseases. Previous and ongoing studies have focused on pharmacokinetic and pharmacodynamic measures of methotrexate activity as therapeutic biomarkers to guide the clinical use of methotrexate. This research has focused on understanding the basic biochemical pharmacology of methotrexate in the treatment of autoimmune disease, and has focused on the role of folates and inflammatory cytokines as biochemical markers of drug efficacy and toxicity. With the increased development and utilization of biologic DMARDs in the treatment of our patients, my group has become increasingly interested in understanding the mechanisms of disposition of these agents in the pediatric population and the utility of therapeutic approaches directed at enhancing exposure and response to this class of drugs. The use of clinical and pre-clinical approaches in my laboratory to address clinically relevant problems provides an ideal environment for students and scientists interested in the translational sciences.
Selected Publications —
Funk, R.S.; Singh, R.; Pramann, L.; Gigliotti, N.; Islam, S.; Heruth, D.P.; Ye, S.Q.; Chan, M.A.; Leeder, J.S.; Becker, M.L. (2016) Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro. Clin Transl Sci, 9, 149-57.
Pramann, L.A.; Davidow, L.W.; van Haandel, L.; Funk, R.S. (2016) Development of Extemporaneously Compounded Aripiprazole Oral Suspensions for Use in Children. Int J Pharm Compd, 20, 257-61.
Funk, R.S.; Becker, M.L. (2016) Disease Modifying Anti-Rheumatic Drugs in Juvenile Idiopathic Arthritis: Striving for Individualized Therapy. Expert Rev Precision Med Drug Dev, 1, 53-68.
Funk, R.S.; van Haandel, L.; Becker, M.L.; Leeder, J.S. (2014) Folate Depletion and Increased Glutamation in Juvenile Idiopathic Arthritis Patients Treated with Methotrexate. Arthritis Rheum, 66, 3476-85.
Funk, R.S.; van Haandel, L.; Becker, M.L.; Leeder, J.S. (2013) Low-dose Methotrexate Results in the Selective Accumulation of Aminoimidazole Carboxamide Ribotide in an Erythroblastoid Cell Line. J Pharm Exp Ther, 347, 154-63.
Kazmi, F.; Hensley, T; Pope, C.; Funk, R.S.; Loewen, G.J.; Buckley, D.B.; Parkinson, A. (2013) Lysosomal sequestration (trapping) of lipophilic amine (cationic amphiphilic) drugs in immortalized human hepatocytes (Fa2N-4 cells). Drug Metab Dispos, 41, 897-905.
Funk, R.S.; Brown, J.T.; Abdel-Rahman, S.M. (2012) Pediatric Pharmacokinetics: Human Development and Drug Disposition. Pediatr Clin North Am, 59, 1001-16.
Logan, R.; Funk, R.S.; Axcell, E.; Krise, J.P. (2012) Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications. Expert Opinion on Drug Metabolism & Toxicology, 8, 943-58.
Funk, R. S.; Krise, J. P. (2012) Cationic amphiphilic drugs cause a marked expansion of apparent lysosomal volume: Implications for a novel intracellular distribution-based drug interaction. Molecular Pharmaceutics, 9, 1384-95.
Goldman, S.G.; Funk, R. S.; Rajewsky, R.A.; Krise, J.P. (2009) Mechanisms of Amine Accumulation in and Egress from, Lysosomes. Bioanalysis, 1, 1445-59.
Funk, R. S.; Krise, J. P. (2007) Exposure of Cells to Hydrogen Peroxide Can Increase the Intracellular Accumulation of Drugs. Molecular Pharmaceutics, 4, 154-9.
Duvvuri, M.; Konkar, S.; Funk, R. S.; Krise, J. M.; Krise, J. P. (2005) A Chemical Strategy to Manipulate the Intracellular Localization of Drugs in Resistant Cancer Cells. Biochemistry, 44, 15743-49.