Ramsey, LB; Prows, CA; Zhang, K; Saldana, SN; Sorter, MT; Pestian, JP; Wenstrup, RJ; Vinks, AA; Glauser, TA. Implementation of Pharmacogenetics at Cincinnati Childrens Hospital Medical Center Lessons Learned Over 14 Years of Personalizing Medicine. Clinical Pharmacology and Therapeutics. 2019; 105(1):49-52.
This study describes the development and implementation of a multidisciplinary Genetic Pharmacology Service at Cincinnati Childrens, designed for practicing clinicians’ point-of-care use, and one of the first of its kind in the country. Since 2004 the GPS has helped to improve therapy in over 30,000 patients by providing dosing suggestions based on a patient's genetic make up.
Euteneuer, JC; Kamatkar, S; Fukuda, T; Vinks, AA; Akinbi, HT. Suggestions for Model-Informed Precision Dosing to Optimize Neonatal Drug Therapy. Journal of Clinical Pharmacology. 2019; 59(2):168-176.
Evidence for dosing, efficacy, and safety of most medications used to treat neonates is sparse. This manuscript highlights aspects of drug response and how it is impacted by prematurity, assesses pharmacogenomic studies in neonates, and offers suggestions for innovative pharmacokinetic/pharmacodynamic model-based approaches that combine population- or physiology-based pharmacology data, Bayesian analysis, and electronic decision support tools for precision dosing in neonates while illustrating examples where this approach can be used to optimize medical therapy in neonates.
Hahn, D; Emoto, C; Euteneuer, JC; Mizuno, T; Vinks, AA; Fukuda, T. Influence of OCT1 Ontogeny and Genetic Variation on Morphine Disposition in Critically Ill Neonates Lessons From PBPK Modeling and Clinical Study. Clinical Pharmacology and Therapeutics. 2019; 105(3):761-768.
This study characterized the ontogeny and pharmacogenetics of the transporter OCT1 and its effects on morphine pharmacokinetics using clinical study data, and advanced physiologically-based pharmacokinetic (PBPK) modeling. This study provides important new knowledge that will facilitate individualized dosing in the neonatal population.
Mizuno, T; O'Brien, MM; Vinks, AA. Significant effect of infection and food intake on sirolimus pharmacokinetics and exposure in pediatric patients with acute lymphoblastic leukemia. European Journal of Pharmaceutical Sciences. 2019; 128:209-214.
This study highlights within-patient fluctuations in sirolimus concentrations associated with intercurrent infection and with changes in diet. These findings highlight the importance of active therapeutic management to ensure maintaining a safe and effective target sirolimus concentration as a patient's clinical status changes.
Kaplan, JM; Zingarelli, B; Krallman, K; Girdwood, ST; Lagory, D; Mizuno, T; Fei, L; Wong, HR; Vinks, AA. Phase 1 safety and pharmacokinetic study on the use of pioglitazone in critically ill patients with sepsis a randomized clinical trial. Intensive Care Medicine. 2018; 44(11):2006-2008.
This is the first model-informed clinical study to investigate pioglitazone as a potential sepsis therapy during critical illness. The study findings highlight that pioglitazone is safe when administered to critically ill pediatric patients, and pioglitazone exposure was associated with a reduction in inflammatory mediators such as IL-6, IL-8 and TNF-alpha.