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Maturation of the various path- ways involved in drug metabolism occurs at variable rates over the first weeks of life 160 mg tricor, and recovery from perinatal injury improves hepatic and renal function order tricor 160 mg amex. Overall, there is a dramatic increase in the ability to eliminate the commonly used anticonvul- sant drugs, so that changes in dosing are required to maintain therapeutic drug levels over the first weeks of life. When anticonvulsant treatment is indicated, phenobarbital is the drug most commonly used as first-line therapy. Other first-line options include benzodiazepines (diazepam, lorazepam), and phenytoin or, if available, its prodrug fosphenytoin. There have been few studies comparing the efficacy of these drugs in the treatment of neonatal seizures. Typical initial doses of the first-line drugs are provided in Table 3, and additional discussion of the individual drugs is given below. Phenobarbital: Phenobarbital affects GABAA receptors to enhance GABA- related inhibition. It may also inhibit excitatory amino acid transmission and block voltage-activated calcium currents. Phenobarbital is subject to protein binding, and it is the unbound (free), unionized fraction that is active. Alterations in acid–base balance in the newborn may impact efficacy of the drug for this reason. Its half-life is long, from 100 to 300 hr, or longer in prema- ture infants, but declines to 100 hr or less over the first weeks of life. An initial intra- venous (IV) loading dose of 20 mg=kg may be followed by increments of 5–10 g=kg IV to a total of 40 g=kg, with higher doses associated with improved efficacy.
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