PubMed Health⌕ Search

Biomedical subjects

D Haidukewych

Publications and source records attributed to D Haidukewych.

25 records · Page 2Linked to original sources
PubMed1982

Monitoring free valproic acid in epilepsy patients medicated with coanticonvulsants.

Methodology for monitoring free valproic acid (VPA) and experimental proof of intrapatient in vivo diurnally and disproportionately variable free VPA fractions has recently been reported. An inherent assumption in accepting therapeutic VPA plasma levels to be 50-100 micrograms/ml is that free fractions remain constant. This assumption is no longer tenable. Therefore, monitoring only VPA plasma levels could be misleading. The serial 9-h time-course (7 a.m. 0 10-1-4 p.m.) of free versus plasma VPA levels was investigated in 24 patients. Limits for diurnal fluctuations were (mean +/- SD): Group A (n = 14); 49.0 mg/kg; multiple equal dosing: Free VPA (micrograms/ml) 6.06 (1.55 to 12.62 (4.89), plasma VPA (micrograms/ml) 52.9 (11.6) to 84.2 (21.3), percent free VPA 11.5 (1.8) to 14.9 (2.5). Group B (n = 10); 30.6 mg/kg; b.i.d.: 12.0 (2.4) mg/kg a.m. and 18.7 (3.3) mg/kg p.m.: Free VPA 5.53 (1.04) to 9.92 (1.51), plasma VPA 52.0 (7.3) to 79.2 (9.6), percent free VPA 10.7 (1.6) to 12.5 (0.8). Reducing the dosage by 19 mg/kg (A to B) decreased VPA plasma levels by 6.9% nd free VPA levels by 28.9%. For B: y = 8.15 + 4.03 x; n = 10, r = 0.954, Sy.x = 1.38, when x = steady-state (7 a.m.) free VPA concentration and y = VPA mg/kg/day. The findings suggest that multiple dosing is unnecessary. Similar plasma levels with far less diurnal fluctuations of free levels are achievable by a smaller drug dose with approximately two-thirds of total daily dose being administered in the evening and one-third in the morning.

Adult↗
PubMed1982

Monitoring octanoic and decanoic acids in plasma from children with intractable epilepsy treated with medium-chain triglyceride diet.

We describe a procedure for gas-chromatographic determination of n-octanoic and n-decanoic acids in 100 microL of plasma from children with intractable epilepsy treated with medium-chain triglyceride (MCT) diet. With n-nonanoic acid as the internal standard, the extraction efficiencies for octanoic and decanoic acids were 98 and 105%, respectively. Within-run CVs for octanoic acid at 0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 micrograms/0.1 mL were 8.8, 7.9, 8.5, 6.5, 4.3, and 5.7%, respectively. For decanoic acid at identical concentrations, the CVs were 10.0, 7.4, 4.9, 4.0, 2.6, and 3.5%, respectively. For 10 children on MCT diet (45.9% of calories supplied as MCT) the mean concentrations of octanoic and decanoic acids were 44.2 and 27.0 mg/L, respectively. Presence of relatively "high" quantities of these acids in plasma may contribute to seizure control when MCT diet is prescribed for intractable childhood epilepsy.

Caprylates↗
PubMed1981

Dissociation between free and bound phenytoin levels in presence of valproate sodium.

A dissociation of free vs bound phenytoin levels is frequently observed in the presence of therapeutic doses of valproate sodium. This leads at times to symptoms and signs of phenytoin intoxication despite "therapeutic" plasma levels. The importance of supplementing bound levels with free levels is stressed when combined therapy of this type is used in epileptic patients.

Adult↗
PubMed1981

Serial free and plasma valproic acid and phenytoin monitoring and drug interactions.

In 12 institutionalized epilepsy patients who had been treated 19 months (SD +/- 5) with valproic acid, 27.0 mg/kg (SD +/- 11.9), phenytoin, 6.33 mg/kg (SD +/- 1.36), and co-anticonvulsants, the mean percentage of daily free valproic acid was 11.72 (SD +/- 2.10) and of phenytoin 20.39 (SD +/- 3.32). By serial within-day blood samplings for a.m., noon, and p.m. periods, the diurnal variation of percentage free valproic acid and phenytoin was determined for each patient. For morning and noon periods the variations in the percentages of free valproic acid and phenytoin were independent of each other, correlation coefficients (r) being zero for each period. In contrast, for early p.m. the correlation coefficient was highly significant at r = 0.894 (p less than 0.01). It is apparent that diurnal variations in the percentages of free valproic acid and phenytoin occur even in patients who have been treated with these compounds for more than a year.

Adolescent↗
PubMed1980

Monitoring clorazepate dipotassium as desmethyldiazepam in plasma by electron-capture gas--liquid chromatography.

We describe a procedure for determing clorazepate dipotassium as its decarboxylated, pharmacologically active metabolite, desmethyldiazepam, in 100 microL of plasma, with use of electron-capture gas--liquid chromatography and with methylnitrazepam as the internal standard. The procedure is a one-tube, one-step extraction without derivative formation and is accurate, reproducible, and rapid. The sensitivity limit is 20 micrograms/L. Within-run and between-run CV's (concentration, 3.5 mg/L) were 2.9 and 3.5%, respectively. Within-run CV's for 1.5 and 1.0 mg/L concentrations were 3.9 and 4.3%, respectively. For a 1.0 mg/kg per day dose of clorazepate dipotassium, the mean steady-state concentration of desmethyldiazepam in plasma was 1.037 mg/L.

Anti-Anxiety Agents↗
PubMed1980

Monitoring 2-ethyl-2-phenylmalonamide in serum by gas-liquid chromatography: application to retrospective study in epilepsy patients dosed with primidone.

We describe a procedure for determining 2-ethyl-2-phenylmalonamide (I) in serum of epilepsy patients dosed with primidone (II) for seizure control, by extracting the sample with chloroform under basic conditions, with use of an internal standard, 2-ethyl-2-(p-tolyl)malonamide, and without derivative formation. The sensitivity limit is 1.0 mg/L. Within-run CVs for 5, 10, and 30 mg/L concentrations were 3.5, 2.5, and 0.7%, respectively. For a 1.0 mg/kg body wt per day dose of II in patients co-medicated with phenytoin (Group A), the mean steady-state concentrations of I, II, and phenobarbital (III) were 0.72, 0.62, and 2.24 mg/L, respectively. For patients co-medicated with carbamazepine and phenytoin (Group B), I, II, and III concentrations were 0.68, 0.44, and 2.12 mg/L, respectively. Between these groups, only for II were the concentrations statistically different (t = 2.762; p < 0.01). For Group A no correlation was found between II and III. For Groups A and B, the coefficients of correlation between I and III were 0.626 and 0.826, respectively.

Adult↗