“The Controversy over Generic Antiepileptic Drugs”,1 which appears in this issue, reviews bioequivalence test procedures of antiepileptic drug (AED) formulations. This review, by Shaw and Hartman, points out the variability in the pharmacokinetic properties of many AED formulations. They conclude that drug concentrations between the standard brand name formulation and any one generic product are likely to be minimal, but generic-to-generic comparisons are more likely to produce clinically important differences. While these different formulations may be clinically relevant to only a small percent of patients, a seizure can have a substantial impact on a patient's life. The authors

ABSTRACT

This article describes the history of the Pediatric Pharmacy Advocacy Group (PPAG). From its humble beginning in 1979, to its formation as the Pediatric Directors of Pediatric Hospitals in 1985, through its time as the Pediatric Pharmacy Administrative Group and through its evolution into the PPAG. The organization was established and continues to be dedicated to improving medication therapy use in children. Its sole purpose is to promote safe and effective medication use in children through communication, education, and research. After three decades, PPAG has established itself as the preeminent pediatric pharmacy organization. Its annual conference has grown over the years to become the best educational and networking meeting for pediatric pharmacists worldwide.

ABSTRACT

As patent protection ends for the next generation of antiepileptic drugs (AEDs), a complex debate continues over generic substitution of AEDs. On one hand, generic drug formulations provide cost savings for patients and society. On the other hand, patients with epilepsy and physicians are wary about the adequacy and efficacy of the Food and Drug Administration's (FDA) standards for generics. This article reviews current and proposed bioequivalence test procedures, summarizes new generic AED formulations and their costs, and discusses potential pitfalls in the current standards. These shortcomings include certain pharmacokinetic factors and clinical pharmacologic factors that may affect bioequivalence of generic AEDs, and statistical limitations of the standards. While the drug concentration differences between the brand name drug and each generic formulation are unlikely to be substantial, the differences with generic-to-generic switches will be greater and potentially clinically significant. Conversely, owing to their more favorable pharmacokinetic profile, newer AEDs may be less prone to problems with generic substitution than older ones. Unfortunately, very few data are available to guide decisions regarding what is best for an individual patient. Based on new prediction methods, generic substitution should be safe for many patients but identifying them ultimately requires more rigorous study.

ABSTRACT

OBJECTIVES

To review pharmacokinetics in obese children and to provide medication dosing recommendations.

METHODS

EMBASE, MEDLINE, and International Pharmaceutical Abstracts databases were searched using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, drug, dose, kidney function test, creatinine, pediatric, and child.

RESULTS

We identified 10 studies in which the authors examined drug dosing or pharmacokinetics for obese children. No information was found for drug absorption or metabolism. Obese children have a higher percent fat mass and a lower percent lean mass compared with normal-weight children. Therefore, in obese children, the volume of distribution of lipophilic drugs is most likely higher, and that of hydrophilic drugs is most likely lower, than in normal-weight children. Serum creatinine concentrations are higher in obese than normal-weight children. Total body weight is an appropriate size descriptor for calculating doses of antineoplastics, cefazolin, and succinylcholine in obese children. Initial tobramycin doses may be determined using an adjusted body weight, although using total body weight in the context of monitoring serum tobramycin concentrations would also be an appropriate strategy. We found no information for any of the opioids; antibiotics such as penicillins, carbapenems, vancomycin, and linezolid; antifungals; cardiac drugs such as digoxin and amiodarone; corticosteroids; benzodiazepines; and anticonvulsants. In particular, we found no information about medications that are widely distributed to adipose tissue or that can accumulate there.

CONCLUSIONS

The available data are limited because of the small numbers of participating children, study design, or both. The number and type of drugs that have been studied limit our understanding of the pharmacokinetics in obese children. In the absence of dosing information for obese children, it is important to consider the nature and severity of a child's illness, comorbidities, organ function, and side effects and physiochemical properties of the drug. Extrapolating from available adult data is possible, as long as practitioners consider the effects of growth and development on the pharmacokinetics relevant to the child's age.