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. 1992 Sep;34(3):231–235. doi: 10.1111/j.1365-2125.1992.tb04129.x

Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.

S D Ferrara 1, S Zotti 1, L Tedeschi 1, G Frison 1, F Castagna 1, L Gallimberti 1, G L Gessa 1, P Palatini 1
PMCID: PMC1381393  PMID: 1389947

Abstract

1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.

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Selected References

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  1. Andén N. E., Stock G. Inhibitory effect of gammahydroxybutyric acid and gammaaminobutyric acid on the dopamine cells in the substantia nigra. Naunyn Schmiedebergs Arch Pharmacol. 1973;279(1):89–92. doi: 10.1007/BF00502071. [DOI] [PubMed] [Google Scholar]
  2. Arena C., Fung H. L. Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption. J Pharm Sci. 1980 Mar;69(3):356–358. doi: 10.1002/jps.2600690331. [DOI] [PubMed] [Google Scholar]
  3. BESSMAN S. P., SKOLNIK S. J. GAMMA HYDROXYBUTYRATE AND GAMMA BUTYROLACTONE: CONCENTRATION IN RAT TISSUES DURING ANESTHESIA. Science. 1964 Mar 6;143(3610):1045–1047. doi: 10.1126/science.143.3610.1045. [DOI] [PubMed] [Google Scholar]
  4. Conn H. O. A peek at the Child-Turcotte classification. Hepatology. 1981 Nov-Dec;1(6):673–676. doi: 10.1002/hep.1840010617. [DOI] [PubMed] [Google Scholar]
  5. Fadda F., Argiolas A., Melis M. R., De Montis G., Gessa G. L. Suppression of voluntary ethanol consumption in rats by gamma-butyrolactone. Life Sci. 1983 Mar 28;32(13):1471–1477. doi: 10.1016/0024-3205(83)90913-x. [DOI] [PubMed] [Google Scholar]
  6. Fadda F., Colombo G., Mosca E., Gessa G. L. Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats. Alcohol Alcohol. 1989;24(5):447–451. [PubMed] [Google Scholar]
  7. GIARMAN N. J., ROTH R. H. DIFFERENTIAL ESTIMATION OF GAMMA-BUTYROLACTONE AND GAMMA-HYDROXYBUTYRIC ACID IN RAT BLOOD AND BRAIN. Science. 1964 Aug 7;145(3632):583–584. doi: 10.1126/science.145.3632.583. [DOI] [PubMed] [Google Scholar]
  8. Gallimberti L., Canton G., Gentile N., Ferri M., Cibin M., Ferrara S. D., Fadda F., Gessa G. L. Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet. 1989 Sep 30;2(8666):787–789. doi: 10.1016/s0140-6736(89)90842-8. [DOI] [PubMed] [Google Scholar]
  9. LABORIT H., JOUANY J. M., GERARD J., FABIANI F. [Summary of an experimental and clinical study on a metabolic substrate with inhibitory central action: sodium 4-hydroxybutyrate]. Presse Med. 1960 Nov 12;68:1867–1869. [PubMed] [Google Scholar]
  10. Lettieri J. T., Fung H. L. Dose-dependent pharmacokinetics and hypnotic effects of sodium gamma-hydroxybutyrate in the rat. J Pharmacol Exp Ther. 1979 Jan;208(1):7–11. [PubMed] [Google Scholar]
  11. Lettieri J., Fung H. L. Improved pharmacological activity via pro-drug modification: comparative pharmacokinetics of sodium gamma-hydroxybutyrate and gamma-butyrolactone. Res Commun Chem Pathol Pharmacol. 1978 Oct;22(1):107–118. [PubMed] [Google Scholar]
  12. Mamelak M., Scharf M. B., Woods M. Treatment of narcolepsy with gamma-hydroxybutyrate. A review of clinical and sleep laboratory findings. Sleep. 1986;9(1 Pt 2):285–289. doi: 10.1093/sleep/9.1.285. [DOI] [PubMed] [Google Scholar]
  13. Pol W., Kleijn E., Lauw M. Gas chromatographic determination and pharmacokinetics of 4-hydroxybutrate in dog and mouse. J Pharmacokinet Biopharm. 1975 Apr;3(2):99–113. doi: 10.1007/BF01066018. [DOI] [PubMed] [Google Scholar]
  14. Roth R. H., Nowycky M. C. Dopaminergic neurons: effects elicited by gamma-hydroxybutyrate are reversed by picrotoxin. Biochem Pharmacol. 1977 Nov 1;26(21):2079–2082. doi: 10.1016/0006-2952(77)90022-3. [DOI] [PubMed] [Google Scholar]
  15. Shumate J. S., Snead O. C., 3rd Plasma and central nervous system kinetics of gamma-hydroxybutyrate. Res Commun Chem Pathol Pharmacol. 1979 Aug;25(2):241–256. [PubMed] [Google Scholar]
  16. Snead O. C., 3rd, Furner R., Liu C. C. In vivo conversion of gamma-aminobutyric acid and 1,4-butanediol to gamma-hydroxybutyric acid in rat brain. Studies using stable isotopes. Biochem Pharmacol. 1989 Dec 15;38(24):4375–4380. doi: 10.1016/0006-2952(89)90645-x. [DOI] [PubMed] [Google Scholar]
  17. Snead O. C., 3rd, Morley B. J. Ontogeny of gamma-hydroxybutyric acid. I. Regional concentration in developing rat, monkey and human brain. Brain Res. 1981 Jul;227(4):579–589. doi: 10.1016/0165-3806(81)90010-9. [DOI] [PubMed] [Google Scholar]
  18. Stadler H., Lloyd K. G., Bartholini G. Dopaminergic inhibition of striatal cholinergic neurons: synergistic blocking action of gamma-butyrolactone and neuroleptic drugs. Naunyn Schmiedebergs Arch Pharmacol. 1974;283(2):129–134. doi: 10.1007/BF00501139. [DOI] [PubMed] [Google Scholar]
  19. Vayer P., Mandel P., Maitre M. Gamma-hydroxybutyrate, a possible neurotransmitter. Life Sci. 1987 Sep 28;41(13):1547–1557. doi: 10.1016/0024-3205(87)90721-1. [DOI] [PubMed] [Google Scholar]
  20. Vree T. B., van der Kleijn E. Rapid determination of 4-hydroxybutyric acid (Gamma OH) and 2-propyl pentanoate (Depakine) in human plasma be means of gas-liquid chromatography. J Chromatogr. 1976 Jun 9;121(1):150–152. doi: 10.1016/s0021-9673(00)82317-1. [DOI] [PubMed] [Google Scholar]
  21. Walters J. R., Roth R. H., Aghajanian G. K. Dopaminergic neurons: similar biochemical and histochemical effects of gamma-hydroxybutyrate and acute lesions of the nigro-neostriatal pathway. J Pharmacol Exp Ther. 1973 Sep;186(3):630–639. [PubMed] [Google Scholar]

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