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Phenobarbital Increases the Theophylline Requirement of Premature Infants Being Treated for Apnea FREE

Malektaj Yazdani, MD; Grace E. Kissling, PhD; Tai H. Tran, MD; Sheila K. Gottschalk, MD; Claudia R. Schuth, MD
[+] Author Affiliations

Accepted for publication Aug 18, 1986.

Reprint requests to Department of Pediatrics, Louisiana State University School of Medicine, 1542 Tulane Ave, New Orleans, LA 70112-2822 (Dr Yazdani).


Am J Dis Child. 1987;141(1):97-99. doi:10.1001/archpedi.1987.04460010097036.
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• To determine the effect of phenobarbital sodium therapy and subependymal intraventricular hemorrhage (SEp-IVH) on the theophylline requirement of premature infants suffering with apnea and seizure activity, we compared three groups of patients as follows: group 1, those with apnea of prematurity (ten patients); group 2, those with apnea and SEp-IVH (ten patients); and group 3, those with apnea, SEp-IVH, and seizure activity for which they were receiving phenobarbital therapy (nine patients). Patients in groups 1 and 2 required lower dosages and blood levels of theophylline to control their apnea than did those in group 3, who required higher dosages and blood levels of methylxanthines. Theophylline dosages and blood levels did not significantly differ between groups 1 and 2. In group 3, the theophylline requirement for control of apnea was significantly increased after initiation of phenobarbital therapy. There seems to be a direct correlation between the increased requirement for theophylline and concomitant phenobarbital administration. The data suggest that phenobarbital increases theophylline requirement when treating neonatal apnea.

(AJDC 1987;141:97-99)

REFERENCES

Papile L, Burstein J, Burstein R, et al:  Incidence and evolution of subependymal and intraventricular hemorrhage . J Pediatr 1978;;92: 529-534.
Volpe JJ:  Neonatal seizures , in Volpe JJ (ed): Neurology of the Newborn . Philadelphia, WB Saunders Co, 1981;, pp 115-120.
Fitzpatrick J, McClelland MA:  A simple rapid method for determining theophylline serum by HpLc . Ann Clin Biochem 1983;;70: 123-126.
Booker HE, Darcy BA:  Enzymatic immunoassay vs gas liquid chromatography for determination of phenobarbital and diphenylhydantoin in serum . Clin Chem 1975;:21:1766-1768.
Pagano P, Halvorsen KT:  An algorithm for finding the exact significance levels of rXc contingency tables . J Am Stat Assoc 1981;;76:931-934.
Lohmann SR, Miech RP:  Theophylline metabolism by the rat liver microsomal system . J Pharmacol Exp Ther 1976;;196:213-225.
Neims AH, Warner M, Loughman WM, et al:  Developmental aspects of cytochrome P-450 monoxygenase systems . Ann Rev Pharmacol 1976;;16:427-445.
Bory C, Baltassat P, Porthault M:  Biotransformation of theophylline to caffeine in premature newborn . Lancet 1978;;2:1204-1205.
Brazier JL, Salle B, Rolion B, et al:  In vivo N7 methylation of theophylline to caffeine in premature infants . Dev Pharmacol Ther 1981;;2: 137-144.
Le Messurier DH:  The site of action of caffeine as a respiratory stimulant . J Pharmacol Exp Ther 1936;;57:458-463.
Gautier H, Bonora M:  Effects of hypoxia and respiratory stimulants in conscious intact and carotid denervated cats . Bull Eur Physiopathol Respir 1982;;18:565-582.
Aubier M, Murciano D, Viires N, et al:  Increased ventilation caused by improved diaphragmatic efficiency during aminophylline infusion . Am Rev Respir Dis 1983;;172:148-154.
Goodman Gillman A, Goodman LS, Rail TW, et al: The Pharmacological Basis of Therapeutics . New York, Macmillan Publishing Co Inc, 1985;, pp 351-356.
Whitelaw A, Dubowitz L, Placzek M, et al:  Phenobarbitone for prevention of periventricular hemorrhage in very low birth weight infants . Lancet 1983;;2:1168-1170.

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References

Papile L, Burstein J, Burstein R, et al:  Incidence and evolution of subependymal and intraventricular hemorrhage . J Pediatr 1978;;92: 529-534.
Volpe JJ:  Neonatal seizures , in Volpe JJ (ed): Neurology of the Newborn . Philadelphia, WB Saunders Co, 1981;, pp 115-120.
Fitzpatrick J, McClelland MA:  A simple rapid method for determining theophylline serum by HpLc . Ann Clin Biochem 1983;;70: 123-126.
Booker HE, Darcy BA:  Enzymatic immunoassay vs gas liquid chromatography for determination of phenobarbital and diphenylhydantoin in serum . Clin Chem 1975;:21:1766-1768.
Pagano P, Halvorsen KT:  An algorithm for finding the exact significance levels of rXc contingency tables . J Am Stat Assoc 1981;;76:931-934.
Lohmann SR, Miech RP:  Theophylline metabolism by the rat liver microsomal system . J Pharmacol Exp Ther 1976;;196:213-225.
Neims AH, Warner M, Loughman WM, et al:  Developmental aspects of cytochrome P-450 monoxygenase systems . Ann Rev Pharmacol 1976;;16:427-445.
Bory C, Baltassat P, Porthault M:  Biotransformation of theophylline to caffeine in premature newborn . Lancet 1978;;2:1204-1205.
Brazier JL, Salle B, Rolion B, et al:  In vivo N7 methylation of theophylline to caffeine in premature infants . Dev Pharmacol Ther 1981;;2: 137-144.
Le Messurier DH:  The site of action of caffeine as a respiratory stimulant . J Pharmacol Exp Ther 1936;;57:458-463.
Gautier H, Bonora M:  Effects of hypoxia and respiratory stimulants in conscious intact and carotid denervated cats . Bull Eur Physiopathol Respir 1982;;18:565-582.
Aubier M, Murciano D, Viires N, et al:  Increased ventilation caused by improved diaphragmatic efficiency during aminophylline infusion . Am Rev Respir Dis 1983;;172:148-154.
Goodman Gillman A, Goodman LS, Rail TW, et al: The Pharmacological Basis of Therapeutics . New York, Macmillan Publishing Co Inc, 1985;, pp 351-356.
Whitelaw A, Dubowitz L, Placzek M, et al:  Phenobarbitone for prevention of periventricular hemorrhage in very low birth weight infants . Lancet 1983;;2:1168-1170.

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