Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction

R. G. Dickinson, R. M. Kluck, W. D. Hooper, M. Patterson, J. B. Chalk, M. J. Eadie

Research output: Contribution to journalArticle

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Abstract

Formation of β-glucuronidase-resistant 'glucuronides' of valproic acid (VPA) by intramolecular rearrangement of biosynthetic valproate glucuronide in vivo was investigated in a patient diagnosed with VPA-associated hepatobiliary and renal dysfunction. Plasma elimination half-life of VPA following cessation of the drug was 13.9 h. At the time of the toxicity, the concentration of conjugated VPA in plasma was very high (36-54% of nonconjugated VPA levels) relative to that in normal patients (2.9%). The fraction of conjugated VPA resistant to β-glucuronidase hydrolysis was 0.28-0.47 in plasma and 0.15-0.42 in urine. The corresponding fraction in urine from normal patients receiving VPA therapy was 0.044. The evidence was consistent with retarded elimination of biosynthetic VPA glucuronide caused by renal and hepatobiliary dysfunction. Consequent prolongation of circulation of VPA glucuronide at the slightly alkaline pH of blood would permit extensive intramolecular rearrangement which is known to be pH-, temperature-, and time-dependent. The biological consequences of the presence of such β-glucuronide-resistant conjugated VPA in vivo are largely unknown.

Original languageEnglish (US)
Pages (from-to)589-593
Number of pages5
JournalEpilepsia
Volume26
Issue number6
StatePublished - 1985
Externally publishedYes

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Glucuronides
Valproic Acid
Kidney
Pharmaceutical Preparations
Glucuronidase
Urine
Half-Life
Hydrolysis
Temperature

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Dickinson, R. G., Kluck, R. M., Hooper, W. D., Patterson, M., Chalk, J. B., & Eadie, M. J. (1985). Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction. Epilepsia, 26(6), 589-593.

Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction. / Dickinson, R. G.; Kluck, R. M.; Hooper, W. D.; Patterson, M.; Chalk, J. B.; Eadie, M. J.

In: Epilepsia, Vol. 26, No. 6, 1985, p. 589-593.

Research output: Contribution to journalArticle

Dickinson, RG, Kluck, RM, Hooper, WD, Patterson, M, Chalk, JB & Eadie, MJ 1985, 'Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction', Epilepsia, vol. 26, no. 6, pp. 589-593.
Dickinson RG, Kluck RM, Hooper WD, Patterson M, Chalk JB, Eadie MJ. Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction. Epilepsia. 1985;26(6):589-593.
Dickinson, R. G. ; Kluck, R. M. ; Hooper, W. D. ; Patterson, M. ; Chalk, J. B. ; Eadie, M. J. / Rearrangement of valproate glucuronide in a patient with drug-associated hepatobiliary and renal dysfunction. In: Epilepsia. 1985 ; Vol. 26, No. 6. pp. 589-593.
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AU - Dickinson, R. G.

AU - Kluck, R. M.

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AU - Chalk, J. B.

AU - Eadie, M. J.

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