Abstract
Four critically injured children receiving large doses of phenobarbitone were studied during hypothermia (30°–31°C) and at normal body temperature. The volume of distribution of phenobarbitone varied from 0.79 to 1.01 litres per kg and the serum té ranged from 36.8 ± 9.4 to 86.2 ± 10.5 hrs. The percentage of dose recovered in urine in 16 days ranged from 40.5 to 65.5 pecrent: 2.7 to 12.4 percent as hydroxyphenobarbitone, 1.7 to 19.7 percent as conjugated hydroxyphenobarbitone, 6.0 to 22.4 percent as phenobarbitone-N-glucoside and 17.8 to 23.1 percent as unchanged drug. After the body temperature was allowed to return to normal the rate of excretion of metabolites increased substantially and the rate of excretion of the unchanged drug decreased markedly. It is concluded that reduction in body temperature influences the volume of distribution, rate of metabolism and excretion of phenobarbitone.
RéSUMé
On a étudié quatre jeunes blessés graves recevant du phenobarbitone à hautes doses en hypothermie (30°–31°C) et à température normale. Le volume de distribution du phénobarbitone a varié de 0.79 à 1.01 litre par kg et la t1/2 sérique s’est située entre 36.8 ± 9.4 et 86.2 ± 10.5 heures. Le pourcentage de la dose recouvrée dans l’urine en 16 jours a été de 40.5 à 65.5 pour cent: 2.7 à 12.4 pour cent sous forme d’hydroxyphenobarbitone, de 1.7 à 19.7 pour cent sous forme d’hydroxyphenobarbitone conjugué, de 6.0 à 22.4 pour cent sous forme de phenobarbitone-N-glucoside et de 17.8 à 23.1 pour cent sous forme inchangée. Lorsqu’on a laissé la température revenir à la normale, la vitesse d’excrétion des métabolites a augmenté substantiellement alors que l’excrétion sous forme inchangée a subit une baisse importante. On en conclut que la baisse de température de l’organisme a influencé le volume de distribution, la vitesse du métabolisme et de l’excrétion du phenobarbitone.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Conn, A.W., Edmonds, J.F. &Barker, G.A. Near-drowning in cold fresh water: Current treatment regimen. Can. Anaesth. Soc. J.25: 259–265 (1978).
Conn, A.W., Edmonds, J.F. &Barker, G.A. Cerebral resuscitation in near-drowning. Pediatric Clinics of North America26: 691–701 (1979).
Conn, A.W., Montes, J.E., Barker, G.A. &Edmonds, J.F. Cerebral salvage in near-drowning following neurological classification by triage. Can. Anaesth. Soc. J.27: 201–210 (1980).
Algeri, E.J. &McBay, A.J. Metabolite of phénobarbital in human urine. Science123: 183–184 (1956).
Borèus, L.O., Jalling, B. &Källberg, N. Phénobarbital metabolism in adults and in newborn infants. Acta Pacdiatr. Scand.67: 193–200 (1978).
Butler, T.C. The metabolic hydroxylation of phénobarbital. J. Pharmacol. Exp. Ther.116: 326–336 (1956).
Heimann, G. &Gladtke, E. Pharmacokinetics of phénobarbital in childhood. Eur J. Clin. Pharmacol.12: 305–310 (1977).
Horning, M.G., Butler, CM., Nowlin, J. &Hill, R.M. Minireview. Drug metabolism in the human neonate. Life Sci.16: 651–672 (1975).
Källberg, N., Agurell, S., Ericsson, O., Bucht, E., Jalling, E. Borèus, L.O. Quantitation of phénobarbital and its main metabolites in human urine. Eur. J. Clin. Pharmacol.9: 161–168 (1975).
Nau, H., Rating, D., Häuser, I., Jäger, E., Koch, S. &Helge, H. Placental transfer and pharmacokinetics of Primidone and its metabolites phénobarbital PEMA and hydroxyphenobarbital in neonates and infants of epileptic mothers. Eur. J. Clin. Pharmacol.18: 31–42 (1980).
Pitlick, W., Painter, M. &Pippenger, C. Phenobarbital pharmacokinetics in neonates. Clin. Pharmacol. Ther.23: 346–350 (1978).
Ravn-Jonsen, A., Lunding, M. &Secher, O. Excretion of phenobarbitone in urine after intake of large doses. Acta Pharmacol. Toxicol.27: 193–301 (1969).
Walson, P.D., Mimaki, T., Curless, R., Mayersohn, M. &Perrier, D. Once daily doses of phénobarbital in children. J. Pediatrics.97: 303–305 (1980).
Tang, B.K., Kalow, W. &Grey, A.A. Metabolic fate of phénobarbital in man. N-glucoside formation. Drug Metab. Dispos.7: 315–318 (1979).
Tang, B.K. &Carro-Ciampi, G. A method for the study of N-glucosidation in vitro amobarbital-N-glucoside formation in incubations with human liver. Biochem. Pharmacol.39: 2085–2088 (1980).
Kinniburgh, D.W. &Boyd, N.D. Phenytoin binding to partially purified albumin in renal disease. Clin. Pharmacol. Ther.29: 203–210 (1981).
Kalow, W., Tang, B.K., Kadar, D. &Inaba, T. Distinctive patterns of amobarbital metabolites in man. Clin. Pharmacol. Ther.24: 576–582 (1978).
Kalow, W., Endrenyi, L., Inaba, T., Kadar, D. &Tang, B.K. Pharmacogenetic investigation of amobarbital disposition. Advances in Pharmacology and Therapeutics, Clinical Pharmacology (ed. P. Duchene-Marullaz)6: 31–40 (1979).
Author information
Authors and Affiliations
Additional information
Supported in part by: The Hospital for Sick Children Foundation, Grant No. 79-63R, and MRC of Canada MA-5799.
Rights and permissions
About this article
Cite this article
Kadar, D., Tang, B.K. & Conn, A.W. The fate of phenobarbitone in children in hypothermia and at normal body temperature. Canad. Anaesth. Soc. J. 29, 16–23 (1982). https://doi.org/10.1007/BF03007942
Issue Date:
DOI: https://doi.org/10.1007/BF03007942