What dosing adjustments should be made to medications in children who are morbidly obese and weigh as much as an adult? Should I stop at the maximum dose for a child of “normal” weight?
—Judy Snow, MS, ARNP-C, Lakeland, Fla.

As a rule of thumb, never prescribe more than the maximum adult dose for a child, even if the weight/kg dose would be greater. For example, a child weighing 70 kg who has otitis media would usually be dosed at 90 mg/kg amoxicillin. The calculated dose would be 6,300 mg/day (in divided doses). The maximum adult dose is 3,000 mg. However, there are additional things to consider in the obese child or adolescent.

Increased adipose tissue alters the disposition of drugs in the body. The pharmacokinetic properties of absorption, distribution, metabolism, and elimination must be considered. Preliminary studies in adults demonstrate no significant difference in absorption in obese and nonobese patients. Volume of distribution is where the most unpredictability occurs. Lipophilic medications may have increased distribution into fatty tissue, thereby decreasing plasma volume and potentially leading to subtherapeutic levels and possibly increased half-life. Protein binding is another factor that influences plasma levels. Obesity can increase the concentration of some of the major plasma proteins. Alpha1-acid glycoprotein and lipoproteins bind with such alkaline drugs as clindamycin (commonly used for methicillin-resistant Staphylococcus aureus skin infections) and propranolol (a common antihypertensive in obese children). Albumin is not increased in obesity. Metabolism can also be affected by adiposity. Phase 1 metabolism via oxidation, reduction, and hydrolysis may be increased, while phase 2 reactions (conjugation by sulfation or glucuronidation) could be a factor in suboptimal therapeutic response. Individualizing drug doses and increased monitoring for therapeutic and toxic effects on liver or kidneys is necessary in obese patients. Unfortunately little research has been conducted in children. For more information, see Orthopedics. 2006;29:984-988.
—Julee B. Waldrop, MS, PNP

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