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The Use of Primidone in Neonates With Theophylline-Resistant Apnea-Reply

Christopher A. Miller, MD; Andrew W. Zimmerman, MD; Mark Gaylord, MD; Vichien Lorch, MD
Arch Pediatr Adolesc Med. 1994;148(3):332-333. doi:10.1001/archpedi.1994.02170030101030.
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We thank özbag for his interest in our article and comments regarding a possible alternative mechanism of action of primidone on theophylline-resistant apnea in preterm infants (effect of phenobarbital, a metabolite).

While he correctly cites data showing an effect of phenobarbital on active sleep (and subsequently on apnea in some infants),1 he fails to note the inconsistency in the usefulness of that drug in neonatal apnea. Phenobarbital has been tried in patients with preterm apnea based on the supposition that apnea represents subclinical seizure activity. However, this met with very limited success. In our own institution, at least one infant failed to respond to phenobarbital yet showed subsequent improvement with primidone therapy.

Of perhaps more importance in addressing this speculative mechanism is the pharmacologic data. As özbag correctly points out, phenobarbital is a byproduct of primidone metabolism. The rapid onset of apnea reduction (within 24 hours of


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