Fluctuations of 10-hydroxy-carbazepine during the day in epileptic patients

May, Theodor W.; Rambeck, B.; Sälke-Kellermann, A.

doi:10.1111/j.1600-0404.1996.tb00016.x

Cited by 16 publications

(3 citation statements)

References 16 publications

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“…It should be noticed that the diurnal fluctuation of the MHD concentration may also have an impact on the tolerability of OXC [18][19][20]. Even if the daily fluctuation of MHD serum levels is generally described as relatively small in most cases, high individual variations are possible [21]. These considerations correspond to our findings concerning the pharmaceutical formulation of OXC.…”

Section: Discussionsupporting

confidence: 83%

Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy

Sattler

Schaefer

May³

2015

Seizure

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Section: Discussionsupporting

confidence: 83%

Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy

Sattler

Schaefer

May³

2015

Seizure

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“…34,35 Clinical response to oxcarbazepine is primarily dependent on its active metabolite MHD, which in experimental models retains pharmacologic activity similar to the parent drug 4 and is found in human plasma at much higher concentrations. [1][2][3] Clinical response may be affected by intra-and interindividual variability in plasma MHD concentrations 3,21,36 under the influence of factors such as age, 37 pregnancy, 6 associated disease, and drugdrug interactions. 2 Because the two enantiomers of MHD exhibit major differences in their rate of formation and/or elimination, 5,6 use of an enantioselective assay is desirable to characterize precisely MHD pharmacokinetics and disposition in different experimental and clinical settings.…”

Section: Discussionmentioning

confidence: 99%

A Novel Enantioselective Microassay for the High-Performance Liquid Chromatography Determination of Oxcarbazepine and Its Active Metabolite Monohydroxycarbazepine in Human Plasma

Mazzucchelli

Franco

Fattore

et al. 2007

Therapeutic Drug Monitoring

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A simple and innovative assay is described that allows the determination of the antiepileptic drug oxcarbazepine and the chiral separation of the two enantiomers of its active metabolite monohydroxycarbazepine (licarbazepine). The assay requires liquid-liquid extraction of the sample (200 microL) into tert-butyl methyl ether and dichloromethane, drying of the organic phase under a nitrogen stream, reconstitution with the mobile phase, and injection in the high-performance liquid chromatography system after filtering. Separation of oxcarbazepine, R-(-)-monohydroxycarbazepine, S-(+)-monohydroxycarbazepine, and the second-step metabolite 10,11-trans-dihydroxycarbamazepine (racemate) is achieved with a Chiralcel ODR column and potassium hexafluorophosphate/acetonitrile as mobile phase. Detection is by ultraviolet absorbance at 210 nm. Standard curves are linear (r2 > or = 0.999) over the range of 0.1 to 25 microg/mL for each analyte with a limit of quantification of 0.1 microg/mL (1 ng injected) for all compounds. Within-day and between-day precision is better than 12% and within-day and between-day accuracy is between 99% and 116% for each compound. These performance characteristics are adequate for pharmacokinetic studies and for therapeutic drug monitoring. However, because the two enantiomers of monohydroxycarbazepine exhibit similar pharmacologic activity, nonenantioselective assays are likely to be more cost-effective for therapeutic drug monitoring purposes.

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“…Enzyme‐inducing AEDs enhance the metabolism of MHD and lower its serum concentrations (McKee et al, 1994; May et al, 2003). Valproic acid displaces MHD from its serum protein binding sites by 11% (May et al, 1996b). Verapamil can decrease serum MHD concentrations by 20% (Krämer et al, 1991) whilst viloxazine increases MHD concentrations by 11% (Pisani et al, 1994).…”

Section: Relevance Of Tdm For Individual Aedsmentioning

confidence: 99%

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

et al. 2008

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SUMMARYAlthough no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.

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Fluctuations of 10-hydroxy-carbazepine during the day in epileptic patients

Cited by 16 publications

References 16 publications

Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy

Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy

A Novel Enantioselective Microassay for the High-Performance Liquid Chromatography Determination of Oxcarbazepine and Its Active Metabolite Monohydroxycarbazepine in Human Plasma

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

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