Systems pharmacology approach leads to precision drug dosing algorithm for neonates, infants and children
A predictive computer model developed at Cincinnati Children’s is helping doctors fine-tune the doses of drugs they give to neonates, infants and children, based on specific measurements on how their bodies metabolize and respond to the drugs.
It is a far better system, says lead author Alexander Vinks, PharmD, PhD, director of Clinical Pharmacology, than the traditional practice of dosing drugs for infants and neonates using a kilogram-to-milligram scale based on a child’s weight -- a scaled-down but inaccurate version of adult doses that are downsized and applied to tinier bodies. “It’s always being a tricky question, one that’s very difficult to predict at any given age: how much of a drug to give to a two-week old infant vs. a year-and-a-half-old toddler,” says Vinks. “The moment a child is born, all these physiological systems kick in, but we haven’t known the pace and maturation levels of various systems until we looked at data from various studies.”
Vinks and colleagues participated in a concentration-controlled clinical trial of sirolimus, a drug increasingly used to treat vascular abnormalities but not extensively studied in children. Researchers started a dose and measured sirolimus levels. Next, enzyme measurements reflective of each patient’s liver enzyme CYP3A activity, known to metabolize drugs, were combined with other data, including the child’s age, weight, gender, ethnicity, height, sirolimus concentrations, dosing regimens and other medications. Data from three studies were combined to create an algorithm – still being refined – to pinpoint accurate drug dosing levels. Findings appeared Feb. 4, 2015, in CPT: Pharmacometrics and Systems Pharmacology.
“It’s a very sophisticated way of using state-of-the-art techniques to tease out data for specific drug doses - a sophisticated way of personalized precision dosing,” according to Vinks. His division is working on similar algorithims for methadone and morphine, and receiving inquiries from the around the world about pediatric doses for other drugs.
