Published Feb. 15, 2017
Clinical Pharmacokinetics

The psychiatric drug loxapine has been effective in the treatment of adults with acute agitation associated with schizophrenia or bipolar disorder. However, its potential impact on pediatric psychiatric health was largely unknown.

Early research into how to conduct clinical trials, however, shows promise, after researchers developed a protocol to support a phase 1 pharmacokinetic study to see if loxapine might be effective in children 10 years and older.

The team was led by senior author Alexander Vinks, PharmD, PhD, director of the Division of Clinical Pharmacology, and division colleague and first author Min Dong, PhD. Collaborators also included pharmaceutical companies based in California and Pennsylvania.

As a psychiatric medication, loxapine is a drug-device combination product administered through inhalation. In adults, it helps to restore the balance of natural chemicals in the brain. One example is dopamine, a neurotransmitter that sends messages between the brain and the body’s nerve cells. It is the body's reward activator.

The study goals were to establish a protocol, and to measure how well researchers could predict the likelihood of achieving the target exposure associated with therapeutic effectiveness in adults.

To do that, the team used a nonlinear mixed-effects population pharmacokinetic model to develop pediatric regimens from adult data, adjusting for targeted age groups and body size. It was a departure from the traditional paradigm in which data on adult dose analysis were insufficient. The trial simulations worked.

“With quantitative modeling and trial simulation we can accurately predict how the drug will behave in children,” say Dong and Vinks. “So this very nicely illustrates how modeling and simulation can assist in the design of informative clinical trials to identify safe and effective doses and dose ranges in children and adolescents.”