Requests by pharmaceutical companies for FDA approval of drugs for treatment of HIV-1 disease in children have lagged behind approval for antiviral drugs in the adult population. For example, ZDV therapy for HIV-1-infected children was approved about 10 years after approval for use in infected adults. FDA recommendations now facilitate, and even require, Phase I/II studies that assess drug safety and pharmacokinetics in the pediatric population. Efficacy data for drugs in children are not mandatory if efficacy has been demonstrated in adults for diseases that have similar etiology. HIV-1 disease in both children and adults results from virus infection and PR inhibitors are effective treatment in adults. Consequently, in contrast to ZDV, approval for pediatric use of ritonavir occurred within 2 years of adult approval, while amprenavir and nelfinavir were approved simultaneously for use in adults and children.
Problems associated with providing antiretroviral drugs to children include the formulation, bioavailability, and pharmacokinetics, which all differ from adults.15 Drugs for the adult population are frequently formulated as capsules or tablets, which are not the optimal form for delivery to young children who may not be able to swallow capsules. Dosages of drugs formulated in capsule or tablet form for adults are difficult to adjust for pediatric patients, while liquid or suspension formulations, which facilitate pediatric dosage, can have poor solubility or unpleasant tastes. In addition, differences between adults and children in hepatic metabolism and renal clearance result in different pharmacokinetics in pediatric patients. For the pediatric population, PR inhibitors were formulated as liquid for ritonavir or as powder for nelfinavir. Initial suspension formulations of indinavir or saquinavir had reduced bioavailability, which has delayed availability of these PR inhibitors for young children.
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