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N Wad

Publications and source records attributed to N Wad.

At least 19 recordsLinked to original sources
PubMed1998

Sensitive high-performance liquid chromatographic method with fluorometric detection for the simultaneous determination of gabapentin and vigabatrin in serum and urine.

Serum concentrations of the antiepileptic drug gabapentin (GBP) are usually determined by high-performance liquid chromatography (HPLC) using UV photometric detection after pre-column derivatization with 2,4,6-trinitrobenzenesulphonic acid. Vigabatrin levels in serum are determined by HPLC using fluorescence detection. Like vigabatrin (VGB), gabapentin has also a primary amine group that easily reacts with o-phthaldialdehyde reagent and produces a fluorescing substance. By the use of fluorometric detection, GBP can be determined more simply, sensitively and simultaneously with VGB. The day-to-day coefficient of variation for the determination of GBP in a pooled serum was 4.0% (n=17; serum concentration, 13.8 micromol/l) and forVGB was 3.1% (n=21; serum concentration, 26.4 micromol/l). The lower limit of detection is 0.5 micromol/l for both drugs and the method is linear up to 500 micromol/l for GBP and 1300 micromol/l for VGB.

Acetates↗
PubMed1997

Carbamazepine: detection of another metabolite in serum, 9 hydroxymethyl-10-carbamoyl acridan.

In this article, the authors discuss 9-hydroxymethyl-10-carbamoyl acridan (9-OH-CBZ), another metabolite of carbamazepine (CBZ) found in serum. The retention time of unconjugated 9-OH-CBZ should be known when using a chromatographic method, because it appears in concentrations varying from one eighth to one third of the CBZ-10,11-epoxide (CBZ-E) concentration and may therefore cause analytical interactions. Liquid chromatography/electrospray mass spectrometry ((LC/ES-MS) in a serum extract identified and confirmed 9-OH-CBZ. The amount of 9-OH-CBZ present as conjugate in serum was between 42% and 65%. The correlation factor values (r) between serum concentrations of 9-OH-CBZ and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (trans-CBZ-diol), CBZ-E, and CBZ in 100 serum samples were 0.77, 0.80, and 0.53, respectively. The origin of 9-OH-CBZ is discussed.

Acridines↗
PubMed1996

Vigabatrin dosing during haemodialysis.

The antiepileptic drug vigabatrin has shown efficacy in the treatment of patients with refractory epilepsy. Unlike many other antiepileptics it is not bound to plasma protein and mainly eliminated by the kidney. Although the therapeutic and toxic serum concentration range is not clearly defined and efficacy and toxicity are not closely correlated with the dose, factors decreasing vigabatrin elimination such as advanced age or renal failure may pose risk of untoward effects. Thus far there are no dose recommendations available for patients on haemodialysis. We report on an epileptic patient who experienced severe, partially reversible renal failure as a consequence of near-drowning. In this patient serum concentrations of vigabatrin were measured repeatedly both during haemodialysis and after partial recovery of renal function. The terminal elimination half-life in this patient was 41 hours during the period of severe renal failure (creatinine clearance < 5 ml/min). As about 60% of vigabatrin was removed from the blood pool by haemodialysis in these patients the antiepileptic should be administered after dialysis. To maintain serum concentrations in the usual range and to control seizure activity only 500 mg vigabatrin every 3 days were necessary.

Anticonvulsants↗
PubMed1992

Analyses of the pattern of therapeutic drug monitoring in a university hospital laboratory. Suitability and performance of the CEDIA assays.

New homogeneous enzyme immunoassays (CEDIA assays) for therapeutic drug monitoring were evaluated on Boehringer Mannheim/Hitachi 704. A fluorescence polarization immunoassay and HPLC were chosen as comparison methods. A good correlation of patient data was observed for both methods (slopes 1.033-1.167). Imprecision within-run and between-day as well as the recovery in control samples of an external quality control survey were excellent and comparable to the routine method. In order to optimize the use of the CEDIA assays also for parameters which are less frequently requested, a parameter-setting for the batch-analyzer COBAS Fara was worked out. Performance of the CEDIA assays on random access analyzers is discussed with regard to the background of a laboratory for clinical chemistry in a University Hospital.

Carbamazepine↗
PubMed1986

Degradation of clonazepam in serum by light confirmed by means of a high performance liquid chromatographic method.

The degradation of clonazepam (CZP) in serum during exposure to light can markedly decrease the concentration of the drug. Decay of CZP was studied after exposure to artificial UV light, sunlight, and room light. Serum was extracted with diethylether at pH 9.1. A reversed-phase (RP-8) column was used, with acetonitrile and water as the mobile phase. CZP was detected at 320 nm. The linearity of this high performance liquid chromatographic method is guaranteed to at least 700 nM. The recovery of CZP was 93%, and the day-to-day coefficients of variation were 7.7% (at 75.0 nM) and 6.0% (at 211.4 nM), respectively.

Benzodiazepinones↗
PubMed1985

Michaelis-Menten kinetics and the steady-state serum phenytoin/hydroxyphenytoin ratio.

The effect of nonlinear kinetics on the steady-state ratio of serum phenytoin (PHT) to total 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) was studied in epileptic patients. In each patient, the ratio increased in a nonlinear fashion in relation to both the PHT dose and the PHT serum level. Patients with longer apparent PHT half-lives (t50%) had a higher PHT/p-HPPH ratio. The t50% was either measured directly and found to correlate well with the patient's calculated Michaelis-Menten parameters (Vmax and Km), or was calculated from Vmax and Km values. A close linear correlation was found between the steady-state PHT/p-HPPH ratio and t50% values, interindividually and intraindividually, i.e., as the t50% increased with increasing PHT concentration in a given patient, the PHT/p-HPPH ratio increased in the same proportion. This indicates a good correlation between the overall Michaelis-Menten kinetics of PHT elimination and the PHT/p-HPPH ratio. A close linear correlation between a wide range of PHT doses and steady-state serum total p-HPPH levels was found, suggesting that when the PHT dose is lower than Vmax, the fraction of PHT undergoing parahydroxylation is constant. It is concluded that if, in a given patient, the p-HPPH level corresponds to the value expected from the PHT dose, it can be assumed that compliance and bioavailability are adequate and that the dose does not exceed Vmax. In that case, the PHT/p-HPPH ratio will provide a good estimate of the t50% of PHT at that particular PHT level.

Adolescent↗
PubMed1984

Simultaneous determination of eleven antiepileptic compounds in serum by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the simultaneous determination of carbamazepine, CGP 10 000 (a common metabolite of carbamazepine and oxcarbazepine), desmethylmephenytoin, 10,11-epoxycarbamazepine, ethosuximide, GP 47 779 (the active metabolite from oxcarbazepine, a new drug made by Ciba-Geigy), mephenytoin, phenylethylmalonamide, primidone, pheneturide, phenobarbital and phenytoin is described. The serum is extracted with ethyl acetate at pH 3.9 and the dried extract is dissolved in 70% ethanol in water and an aliquot is injected into a Hewlett-Packard 1084 B liquid chromatograph. A reversed-phase (RP-8) column is used with acetonitrile and water as the mobile phase. The eluted drugs are detected at 207 nm. The recovery of the compounds varies from 76% to 95% with the day-to-day precision (C.V.) between 3.8% and 9.8%, the within-day precision between 1.8% and 5.8% and run-to-run precision between 1.0% and 2.6%.

Anticonvulsants↗
PubMed1984

Carbamazepine-10,11-diol steady-state serum levels and renal excretion during carbamazepine therapy in adults and children.

Steady-state levels of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZ-E), and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZ-diol) were monitored in 53 adults and 16 children, and 24-h urinary excretion of CBZ-E and CBZ-diol was measured in 25 adults and 8 children. The CBZ dose correlated significantly with the serum level of the metabolites but not with the CBZ level. The variability of the CBZ dose/level ratio was related to comedication. Similarly, comedication altered the serum CBZ-diol/CBZ ratio and, to a lesser extent, the CBZ-E/CBZ as well as the CBZ-diol/CBZ-E ratios. Fluctuations of the CBZ-diol levels during the day were less than half as high as CBZ fluctuations. Children had a higher CBZ dose/level ratio and a relatively lower serum CBZ-diol/CBZ ratio, possibly because they also had a higher renal clearance for CBZ-diol. The fraction of the CBZ dose excreted as urinary CBZ-diol was equal in adults and children (35.2 and 36.2%, respectively). The results of this study suggest that the steady-state serum CBZ-diol/CBZ ratio is a sensitive indicator of enzymatic induction and that it can be useful in determining if unexpected CBZ levels can be attributed to the rate of enzymatic conversion of CBZ.

Adult↗
PubMed1984

Individual and combined antiepileptic and neurotoxic activity of carbamazepine and carbamazepine-10,11-epoxide in mice.

Anticonvulsant effect and neurological toxicity were investigated in mice for carbamazepine (CBZ) and its main metabolites, carbamazepine-10,11-epoxide (CBZ-E) and 10,11-dihydro-10,11-trans-dihydroxy-CBZ. The compounds were first tested separately and the results were expressed in terms of brain concentrations. Brain penetration was very poor for 10,11-dihydro-10,11-trans-dihydroxy-CBZ, which had neither anticonvulsant nor neurotoxic activity. Against maximal electroshock, CBZ was slightly more potent than CBZ-E and both were ineffective against pentylenetetrazole and bicuculline. CBZ and CBZ-E displayed similar neurotoxicity. Combined administration of CBZ and CBZ-E revealed a slightly synergistic interaction with regard to both anticonvulsant and neurotoxic action, the therapeutic index of the mixture being similar to that of CBZ. These results suggest that antiepileptic activity and neurological toxicity of CBZ are proportional to the sum of the concentrations of CBZ and its metabolite CBZ-E. Furthermore, variable levels of CBZ-E in relation to CBZ do not affect the overall therapeutic index. Finally, the results do not indicate that CBZ-E alone has any advantage over CBZ with regard to neurotoxic side-effects and therapeutic index.

Animals↗
PubMed1979

Pharmacokinetics of phenylethylacetylurea (pheneturide), an old antiepileptic drug.

The pharmacokinetics of pheneturide (a decarboxylation product of phenobarbital), used to prevent psychomotor seizures for many years, was studied in normal human volunteers. To measure the drug in plasma and urine, a highly sensitive and reproducible thin-layer chromatography-reflectance spectrophotometric assay was developed. The results show that pheneturide follows first-order kinetics in the dose range studied. Its half-life after single doses is 54 hr (range 31--90), and its total body clearance (100% nonrenal) is 2.6 liters/hr (range 1.73--3.59). After repetitive administration, half-life is 40 hr (but clearance remains unchanged because of a lower volume of distribution). Because of the long half-life, repetitive administration results in a continuous steady-state level and makes this drug (kinetically) ideal for long-term use.

Anticonvulsants↗