Kinetics of Phenobarbital in Normal Subjects and Epileptic Patients

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 1982 Jan 1

PMID 7128675

Citations 15

Authors

A J Wilensky

P N Friel

R H Levy

C P Comfort

S P Kaluzny

Affiliations

Soon will be listed here.

Abstract

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 10 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 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 +/- 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 normal car reasonably be extrapolated to the epileptic population.

Citing Articles

Phenobarbital and Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis.

Umar Z, Rasool M, Muhammad S, Yousaf S, Nassar M, Ilyas U Cureus. 2023; 15(1):e33695.

PMID: 36788902 PMC: 9922035. DOI: 10.7759/cureus.33695.

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management.

Kirmani B, Au K, Ayari L, John M, Shetty P, DeLorenzo R Aging Dis. 2021; 12(4):1097-1119.

PMID: 34221552 PMC: 8219503. DOI: 10.14336/AD.2021.0302.

Functional Exploration of the Pulmonary NEB ME.

Brouns I, Verckist L, Pintelon I, Timmermans J, Adriaensen D Adv Anat Embryol Cell Biol. 2021; 233:31-67.

PMID: 33950469 DOI: 10.1007/978-3-030-65817-5_4.

Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats.

Yates L, Aleman M, Knych H, Knipe M, Crowe C, Chigerwe M Front Vet Sci. 2020; 7:86.

PMID: 32154280 PMC: 7046625. DOI: 10.3389/fvets.2020.00086.

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

Fan H, Lee H, Chang K, Lee Y, Lai H, Hung P Int J Mol Sci. 2016; 17(8).

PMID: 27490534 PMC: 5000640. DOI: 10.3390/ijms17081242.

References

SOTANIEMI E, Arvela P, Hakkarainen H, Huhti E . The clinical significance of microsomal enzyme induction in the therapy of epileptic patients. Ann Clin Res. 1970; 2(3):223-7. View

JALLING B . Plasma concentrations of phenobarbital in the treatment of seizures in newborns. Acta Paediatr Scand. 1975; 64(3):514-24. DOI: 10.1111/j.1651-2227.1975.tb03873.x. View

Eadie M, Lander C, Hooper W, Tyrer J . Factors influencing plasma phenobarbitone levels in epileptic patients. Br J Clin Pharmacol. 1977; 4(5):541-7. PMC: 1429157. DOI: 10.1111/j.1365-2125.1977.tb00783.x. View

Patel I, Levy R, Cutler R . Phenobarbital--valporic acid interaction. Clin Pharmacol Ther. 1980; 27(4):515-21. DOI: 10.1038/clpt.1980.72. View

Viswanathan C, Booker H, Welling P . Bioavailability of oral and intramuscular phenobarbital. J Clin Pharmacol. 1978; 18(2-3):100-5. DOI: 10.1002/j.1552-4604.1978.tb02428.x. View

Martin P, Bhushan C, Kapur B, Whiteside E, Sellers E . Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: a kinetic approach. Clin Pharmacol Ther. 1979; 26(2):256-64. DOI: 10.1002/cpt1979262256. View

Garrettson L, Dayton P . Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clin Pharmacol Ther. 1970; 11(5):674-9. DOI: 10.1002/cpt1970115674. View

ALVIN J, McHorse T, Hoyumpa A, BUSH M, Schenker S . The effect of liver disease in man on the disposition of phenobarbital. J Pharmacol Exp Ther. 1975; 192(1):224-35. View

JALLING B . Plasma and cerebrospinal fluid concentrations of phenobarbital in infants given single doses. Dev Med Child Neurol. 1974; 16(6):781-93. View

10.

LOUS P . Plasma levels and urinary excretion of three barbituric acids after oral administration to man. Acta Pharmacol Toxicol (Copenh). 1954; 10(2):147-65. DOI: 10.1111/j.1600-0773.1954.tb01332.x. View

11.

Callaghan N, Feely M, DUGGAN F, OCallaghan M, Seldrup J . The effect of anticonvulsant drugs which induce liver microsomal enzymes on derived and ingested phenobarbitone levels. Acta Neurol Scand. 1977; 56(1):1-6. DOI: 10.1111/j.1600-0404.1977.tb01403.x. View

12.

Wilensky A, Levy R, Troupin A . Clorazepate kinetics in treated epileptics. Clin Pharmacol Ther. 1978; 24(1):22-30. DOI: 10.1002/cpt197824122. View

13.

Robinson G, Sellers E, Janecek E . Barbiturate and hypnosedative withdrawal by a multiple oral phenobarbital loading dose technique. Clin Pharmacol Ther. 1981; 30(1):71-6. DOI: 10.1038/clpt.1981.129. View

14.

Remmer H, Siegert M . [Cumulation and elimination of phenobarbital]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1962; 243:479-94. View

15.

Morselli P, Rizzo M, Garattini S . Interaction between phenobarbital and diphenylhydantoin in animals and in epileptic patients. Ann N Y Acad Sci. 1971; 179:88-107. DOI: 10.1111/j.1749-6632.1971.tb46892.x. View

16.

Bertilsson L . Clinical pharmacokinetics of carbamazepine. Clin Pharmacokinet. 1978; 3(2):128-43. DOI: 10.2165/00003088-197803020-00003. View

17.

Neuvonen P, Elonen E . Effect of activated charcoal on absorption and elimination of phenobarbitone, carbamazepine and phenylbutazone in man. Eur J Clin Pharmacol. 1980; 17(1):51-7. DOI: 10.1007/BF00561677. View

18.

Benet L, Galeazzi R . Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci. 1979; 68(8):1071-4. DOI: 10.1002/jps.2600680845. View

19.

Painter M, Pippenger C, Macdonald H, Pitlick W . Phenobarbital and diphenylhydantoin levels in neonates with seizures. J Pediatr. 1978; 92(2):315-9. DOI: 10.1016/s0022-3476(78)80034-1. View