Pharmacokinetics often differ between obese and nonobese children

By Anne Harding

NEW YORK (Reuters Health) - There is no consensus on how best to adjust medication dosage for obese children, the authors of a new systematic review conclude.

Obese children showed "clinically significant pharmacokinetic alterations" for two-thirds of the drugs included in the review, and these alterations often resulted in major differences in drug exposure compared to non-obese children, Dr. Daniel Benjamin of the Duke Clinical Research Institute in Durham, North Carolina and his colleagues found.

They had previously shown that medication dosing in children cannot be extrapolated from data in adults. "It looks like for obesity this is going to be a similar story," he told Reuters Health in a telephone interview. "You can't predict which drugs are going to go sideways on you, and sometimes you are going to give patients too much drug and sometimes you are going to be giving too little...it's just not clear until you do the study."

It is important to understand how excess weight affects pharmacokinetics in kids, the researchers note in their report, published online May 11 in JAMA Pediatrics. A search of the literature for 1970-2012 yielded 20 studies with pharmacokinetic data on 21 drugs, with a median of 10 obese children included in each study (range, 1 to 112). Studies used a variety of dosing approaches, including fixed dose, body weight, or body surface area. The drugs studied included antineoplastics, anticonvulsants, antibiotics, analgesics or anesthetics, respiratory stimulants and an immunosuppressant.

Exposure data for obese children was available for 17 drugs, and 13 drugs included a non-obese group for comparison. There were clinically significant pharmacokinetic alterations for 11 of the drugs (65%), including decreased volume of distribution, increased volume of distribution, decreased clearance, and increased clearance. For five of the drugs (38%), there were "meaningful differences" in exposure between obese and non-obese children; for four of the drugs, exposure was increased in obese children.

None of the studies included drugs for which differences in pharmacokinetics have been seen for obese and non-obese adults, the authors note, such as acute care medications, cardiovascular drugs, anesthesia, and contraceptives.

"All drugs are toxins," Dr. Benjamin said. "They all have risk to them, but only in some patients is the right dosage of a medicine helpful, and if you don't have the dosage right by definition you're not going to be helpful, you're only going to be hurting the patient."

Dr. Benjamin and his colleagues in the Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee have begun conducting pharmacokinetic trials in obese children, with funding from the National Institute for Child Health and Human Development, and will be working with the institute to develop a pharmacokinetics database for obese children, normal-weight children, and obese adults.

In an editorial, Dr. Matthew Gillman and Dr. Jason Black of Harvard Medical School in Boston state: "No single approach to weight-based dosing emerged from this literature; some regimens appear to be susceptible to overdosing and some to underdosing. In the arena of medication dosing, we need much more information about when and how to treat children with obesity differently."

SOURCE: http://bit.ly/1F2psHf and http://bit.ly/1dljt9B

JAMA Pediatr 2015.

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