The effect of carbamazepine on valproic acid disposition in adult volunteers.

Panesar, S. K.; Orr, J M; Farrell, Kevin; Burton, Rw W.; Kassahun, Kelem; Abbott, Fs S.

doi:10.1111/j.1365-2125.1989.tb05372.x

Cited by 22 publications

(5 citation statements)

References 22 publications

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“…increased production of the 4-ene. In accordance with Panesar et al (37), the concentration of 3-keto was increased in the HKM samples during all phases of polytherapy. However, because therapy changed rapidly within a few weeks there might have been interferences from preceding medications.…”

Section: Resultssupporting

confidence: 70%

Establishing individual metabolite patterns for patients on valproate therapy

Kreher

Darius

Wien

2001

Eur. J. Drug Metab. Pharmacokinet.

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The aim of this study was to establish individual metabolic profiles of patients receiving valproate (VPA) mono- or polytherapy in order to estimate inter- and intraindividual variability under normal conditions. Serum levels of VPA and 15 metabolites were measured by gas chromotography/mass spectrometry (GC/MS) with selected ion monitoring (SIM). Because of a huge inter-subject variability, calculating means for large epileptic populations resulted in broad and vague ranges for serum levels of VPA and its metabolites. It therefore remained difficult to recognize any significant alteration in the individual metabolic profile. Over long term periods, within-patient changes appeared to be much less intense than inherent interindividual differences. In epileptics consecutively receiving various forms of polytherapy, alterations in the metabolic profiles occurred. Therefore, integrating different kinds of co-medication into a single polytherapy group seemed to be inadequate. An adult patient on VPA monotherapy, suffering form intrahepatic metastasis and renal insufficiency, showed an extremely altered metabolic pattern, with the 4-ene and the omega-/omega1-metabolites being strongly elevated and the major beta-metabolites (E)-2-ene and (E,E)-2,3'-diene being significantly diminished. We suggest determining the individual metabolic profile, consisting of accessible major and minor metabolites, for every patient when VPA therapy has been started or been modified. The moment any clinical complications arise, the previously obtained specific pattern of the individual can be taken as reference in order to assess the possible presance of significant alterations which might indicate or even cause any severe side effects. There seems to be no need of monitoring metabolite levels of the average patient continuously except for the high risk group (e.g. infants under 3 years age receiving polytherapy) which exhibited the highest between-subject as well as within-patient variability.

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Section: Resultssupporting

confidence: 70%

Establishing individual metabolite patterns for patients on valproate therapy

Kreher

Darius

Wien

2001

Eur. J. Drug Metab. Pharmacokinet.

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“…This value is similar to that reported by Panesar et al . (26) in adult healthy volunteers and by Yukawa et al . (21) in children.…”

Section: Discussionmentioning

confidence: 89%

Valproate population pharmacokinetics in children

Serrano

Sánchez

Otero

et al. 1999

Journal of Clinical Pharmacy and Therapeutics

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“…The anticonvulsant agents phenobarbitone, phenytoin, and carbamazepine either separately or in combination induce the glucuronidation of paracetamol (43) and possibly norcodeine (24). Carbamazepine also induces valproic acid glucuronidation (44). Coadministration of phenobarbitone and phenytoin induces chloramphenicol glucuronidation (45).…”

Section: Xenobiotic Induction and Physiological Perturbation In Humansmentioning

confidence: 99%

Genetic and Environmental Factors Associated with Variation of Human Xenobiotic Glucuronidation and Sulfation

Burchell¹,

Coughtrie²

1997

Environmental Health Perspectives

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Glucuronidation and sulfation are phase 2 metabolic reactions catalyzed by large families of different isoenzymes in man. The textbook view that glucuronidation and sulfation lead to the production of harmless conjugates for simple excretion is not valid. Biologically active and toxic sulfates and glucuronides are produced and leed to adverse drug reactions, including immune hypersensitivity. Considerable variation in xenobiotic conjugation is observed as a result of altered expression of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (STs). Recent cloning and expression of human cDNA encoding UGTs and STs has facilitated characterization of isoform substrate specificity, which has been further validated using specific antibodies and human tissue fractions. The availability of cloned/expressed human enzymes and specific antibodies has enabled the investigation of xenobiotic induction and metabolic disruption leeding to adverse responses. Genetic polymorphisms of glucuronidation and sulfation are known to exist although the characterization and assessment of the importance of these variations are hampered by appropriate ethical studies in men with suitable safe model compounds. Genetic analysis has allowed molecular identification of defects in well-known hyperbilirubinemias. However, full characterization of the specific functional roles of human UGTs and STs requires rigorous kinetic and molecular analyses of the role of each enzyme in vivo through the use of specific antibodies and inhibitors. This will leed to the better prediction of variation of xenobiotic glucuronidation and sulfation in man.

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The effect of carbamazepine on valproic acid disposition in adult volunteers.

Cited by 22 publications

References 22 publications

Establishing individual metabolite patterns for patients on valproate therapy

Establishing individual metabolite patterns for patients on valproate therapy

Valproate population pharmacokinetics in children

Genetic and Environmental Factors Associated with Variation of Human Xenobiotic Glucuronidation and Sulfation

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