Summary
The kinetics of phenobarbital (PB) were evaluated in six normal subjects and six epileptic patients treated with phenytoin or carbamazepine. Each normal subject received three single doses of PB: PB-sodium 130 mg i.v. (IV), PB sodium 130 mg i.m. (IM), and PB acid 100 mg orally (PO), in random order at least one month apart. After IV PB distributive half-lives varied from 0.13 to 0.70 h, disposition half-lives were 75 to 126 h, steady state volume of distribution (Vss) was 0.54±0.03 l/kg, and clearance (CL) was 3.8±0.77 ml/h/kg. Absolute bioavailability of IM PB was 101±13%, of PO PB (corrected for dose) 100±11%. Peak serum PB concentrations were achieved from 2 to 8 h after IM administration, and from 0.5 to 4 h after PO administration. Epileptic patients exhibited similar PB kinetics: disposition half-lives were 77 to 128 h, Vss 0.61±0.05 l/kg, and Cl 3.9±0.76 ml/h/kg. Phenobarbital appears to represent an exception among antiepileptic drugs, in that pharmacokinetic data obtained in normals can reasonably be extrapolated to the epileptic population.
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References
Lous P (1954) Plasma levels and urinary excretion of three barbituric acids after oral administration to man. Acta Pharmacol Toxicol 10: 147–165
Alvin J, McHorse T, Hoyumpa A, Bush MT, Schenker S (1975) The effect of liver disease in man on the disposition of phenobarbital. J Pharmacol Exp Ther 192: 224–235
Buchthal F, Lennox-Buchthal MA (1972) Phenobarbital: Relation of serum concentration to control of seizures. In: Woodbury DM, Penry JK, Schmidt RP (eds) Antiepileptic Drugs. Raven Press, New York, pp 335–343
Butler TC (1978) Some quantitative aspects of the pharmacology of phenobarbital. In: Pippenger CE, Penry JK, Kutt H (eds) Antiepileptic drugs: Quantitative analysis and interpretation. Raven Press, New York, pp 261–271
Morselli PL, Rizzo M, Garrattini S (1971) Interaction between phenobarbital and diphenylhydantoin in animals and in epileptic patients. Ann NY Acad Sci 179: 88–107
Neuvonen PJ, Elonen E (1980) Effect of activated charcoal on absorption and elimination of phenobarbitone, carbamazepine and phenylbutazone in man. Eur J Clin Pharmacol 17: 51–57
Patel IH, Levy RH, Cutler RE (1980) Phenobarbital-valproic acid interaction. Clin Pharmacol Ther 27: 515–521
Strandjord RE, Johannessen SI (1977) Serum levels of phenobarbitone in healthy subjects and patients with epilepsy. In: Gardner-Thorpe C, Janz D, Meinardi, Pippenger CE (eds) Antiepileptic Drug Monitoring. Pitman Medical, London, pp 89–103
Viswanathan CT, Booker HE, Welling PG (1978) Bioavailability of oral and intramuscular phenobarbital. J Clin Pharmacol 18: 100–105
Garrettson LK, Dayton PG (1970) Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clin Pharmacol Ther 11: 674–679
Jalling B (1974) Plasma and cerebrospinal concentrations of phenobarbital in infants given single doses. Dev Med Child Neurol 11: 781–793
Jalling B (1975) Plasma concentrations of phenobarbital in the treatment of seizures in newborns. Acta Paediatr Scand 64: 514–524
Painter MJ, Pippenger C, MacDonald H, Pitlick W (1978) Phenobarbital and diphenylhydantoin in neonates with seizures. J Pediatr 92: 315–319
Martin PR, Kapur BP, Whiteside EA, Sellers EA (1979) Intraveneous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: A kinetic approach. Clin Pharmacol Ther 26: 256–264
Bertilsson L (1978) Clinical pharmacokinetics of carbamazepine. Clin Pharmacokinet 3: 128–143
Wilensky AJ, Levy RH, Troupin AS, Ojemann LM, Friel P (1978) Clorazepate kinetics in treated epileptics. Clin Pharmacol Ther 24: 22–30
Remmer H, Siegert M (1962) Kumulation und Elimination von Phenobarbital. Arch Exp Pathol Pharmakol 243: 479–494
Sotaniemi E, Arvela P, Hakkarainen H, Huhti E (1970) The clinical significance of microsomal enzyme induction in the therapy of epileptic patients. Ann Clin Res 2: 223–227
Callaghan N, Feely M, Duggan F, O'Callaghan M, Seldrup J (1977) The effect of anticonvulsant drugs which induce liver microsomal enzymes on derived and ingested phenobarbitone levels. Acta Neurol Scand 56: 1–6
Eadie MJ, Lander CM, Hooper WD, Tyrer JH (1977) Factors influencing plasma phenobarbitone levels in epileptic patients. Br J Clin Pharmacol 4: 541–547
Friel PN, Troupin AS (1978) Mephenytoin assay by flash-heater ethylation. In: Pippenger CE, Penry JK, Kutt H (eds) Antiepileptic drugs: Quantitative analysis and interpretation. Raven Press New York, pp 352–354
Benet LZ, Galeazzi RL (1979) Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci 68: 1071–1074
Robinson GM, Sellers EM, Janecek E (1981) Barbiturate and hypnosedative withdrawal by a multiple oral phenobarbital loading dose technique. Clin Pharmacol Ther 30: 71–76
Frösher W (1979) Treatment of status epilepticus. University Park Press, Baltimore
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Wilensky, A.J., Friel, P.N., Levy, R.H. et al. Kinetics of phenobarbital in normal subjects and epileptic patients. Eur J Clin Pharmacol 23, 87–92 (1982). https://doi.org/10.1007/BF01061382
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DOI: https://doi.org/10.1007/BF01061382