Search PubMed⌕ Search

Biomedical subjects

R Hartley

Publications and source records attributed to R Hartley.

At least 55 records · Page 3Linked to original sources
PubMed1991

Dissolution and relative bioavailability of two carbamazepine preparations for children with epilepsy.

The in-vitro dissolution profiles of two carbamazepine formulations (Tegretol and a generic carbamazepine) have been assessed and the bioavailability of carbamazepine compared in 12 epileptic children at steady-state. Dissolution from the generic formulation (100 and 200 mg tablets) tended to be greater than for the proprietary tablets. However, the bioavailability and pharmacokinetics of carbamazepine when assessed at steady-state were similar for the two formulations. It appears, therefore, that the breakthrough seizures and higher incidence of neurological side-effects observed when children were given generic carbamazepine in place of the proprietary formulation cannot be accounted for by differences in bioavailability or pharmacokinetics.

Adolescent↗
PubMed1991

Daily variations in steady-state plasma concentrations of carbamazepine and its metabolites in epileptic children.

Total plasma carbamazepine, carbamazepine-10,11-epoxide (CBZ-EP) and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (CBZ-DIOL) concentrations were measured during a 24h period in 21 patients receiving carbamazepine monotherapy, in equally divided doses, every 12h. Interdose and diurnal variations in plasma concentrations of parent drug and metabolites were assessed. Carbamazepine and both metabolites showed significant differences in mean 4h post-dose plasma concentrations between day and night dosing (p less than 0.001). Significant linear correlations were obtained between carbamazepine dose and plasma concentrations of carbamazepine, CBZ-EP and CBZ-DIOL when sampling times were standardised (p less than 0.01). Comparisons of plasma concentrations of the parent compound with those of its 2 main metabolites revealed significant linear correlations in all cases (p less than 0.01). The effects of daily fluctuations in plasma concentrations of all 3 compounds on their relative concentrations (CBZ-EP:carbamazepine, CBZ-DIOL:carbamazepine and CBZ-DIOL:CBZ-EP) during the 24h period were also determined: the plasma concentration ratios CBZ-EP:carbamazepine and CBZ-DIOL:carbamazepine were significantly related to the dose of carbamazepine at fixed sampling times (p less than 0.05, with 1 exception). The large interdose and diurnal variation in plasma carbamazepine concentrations observed in this study (approximately 40% decrease from peak to trough) has important implications both clinically and in relation to therapeutic drug monitoring.

Adolescent↗
PubMed1990

An ultrastructural study of the exoerythrocytic schizonts of Plasmodium cynomolgi and P. knowlesi in Macaca mulatta.

Exoerythrocytic schizonts of Plasmodium cynomolgi and P. knowlesi were examined by electron microscopy in biopsy samples of primate livers. With maturity the parasitophorous vacuole membrane becomes highly sculptured by the addition of a discontinuous dense thickening, the distribution of which can be a distinguishing character between these two species. The parasitophorous vacuole membrane follows the contours of the parasite faithfully with a minimal surrounding vacuole. The marked destruction of the cytoplasm of the host hepatocyte by most of the parasites studied however gave the distinct, but erroneous, appearance of a large parasitophorous vacuole at the light microscope level. The mature parasite often exhibited a highly invaginated surface contour with the result that the cytoplasm of the host cell and parasite became intimately interdigitated, this interweaving is unlikely to be recognized in light microscopic studies.

Animals↗
PubMed1990

Factors influencing plasma level/dose ratios of carbamazepine and its major metabolites in epileptic children.

The relationship between daily dose and plasma concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZ-EP), and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZ-DIOL) was investigated in 21 children aged 7-16 years who received CBZ monotherapy, twice daily in equally divided doses. Significant linear correlations between CBZ dose and plasma levels were obtained for CBZ and its metabolites (p less than 0.01). In addition, the effects of daily dose and patients' age on the plasma level/dose ratios for CBZ, CBZ-EP, and CBZ-DIOL were evaluated. A significant negative correlation was observed between the daily dose of CBZ and the CBZ plasma level/dose ratio (p less than 0.01). By contrast, plasma level/dose ratios for CBZ-EP and CBZ-DIOL were independent of dose (p greater than 0.1). On the basis of these observations, we consider that the decrease in CBZ plasma level/dose ratio with increasing CBZ dose appears to be due to dose-dependent metabolic clearance of CBZ. The influence of age on plasma level/dose ratios for CBZ and its metabolites was not significant (p greater than 0.05). However, there was considerable interdose and diurnal variation in the plasma level/dose ratios, particularly for CBZ (28-41%); this must be taken into account when making dose adjustments based on plasma level/dose ratios.

Adolescent↗
PubMed1990

Slow release carbamazepine in treatment of poorly controlled seizures.

Thirty three children with poorly controlled epilepsy, and six new patients, were treated with slow release carbamazepine. Twelve of the former had a reduction in the number of seizures of more than half, and 10 had fewer side effects. Three of the new patients stopped having seizures. Variations in plasma concentrations between doses was significantly less when patients took the slow release preparation (22%) compared with the standard preparation (41%). Slow release carbamazepine may improve the conditions of children whose seizures are poorly controlled.

Adolescent↗
PubMed1990

Breakthrough seizures with generic carbamazepine: a consequence of poorer bioavailability?

The bioavailability of carbamazepine from two products (Ethical Generics and Ciba-Geigy) and their efficacy with regard to seizure control and incidence of side-effects were compared in 23 children with tonic-clonic or complex partial seizures. Mean plasma concentrations of carbamazepine, carbamazepine 10, 11-epoxide and 10,11-dihydro-10, 11-trans-dihydroxy-carbamazepine at comparable sampling times were not significantly different during treatment with the two drug preparations. The incidence of seizures and occurrence of abnormal EEGs were not significantly different during treatment with the two carbamazepine preparations, and, in addition, the overall incidence of side-effects was not significantly different during the two treatment periods. However, neurological side-effects were significantly less during treatment with the Ciba-Geigy product. On the basis of these observations we are confident that the efficacy of these two carbamazepine preparations in children at steady-state is the same.

Adolescent↗
PubMed1989

A rapid and specific HPLC-electrochemical method for the determination of endogenous 5-methyltetrahydrofolic acid in plasma using solid phase sample preparation with internal standardization.

A rapid and specific HPLC-electrochemical method for determining endogenous 5-methyltetrahydrofolic acid (5MeTHF) in plasma is described. Quantitative solid phase extraction of 5MeTHF and internal standard, beta-hydroxyethyltheophylline, was carried out using proprietary phenyl bonded-silica columns (Bond Elut Phenyl cartridges, 1.0 mL capacity). Chromatographic separation was achieved using a mobile phase consisting of 15% (v/v) methanol in 0.05 M KH2PO4, pH 3.5 at a flow rate of 2.0 mL/min in conjunction with a Waters Assoc. radially compressed Nova-Pak phenyl column (10 cm x 8 mm, 4 microns bonded silica). The internal standard was measured by UV detection at 254 nm. A Bioanalytical Systems Inc. LC-17 glassy carbon oxidative flow cell with a potential held at +0.35 V vs Ag/AgCl using the LC-4A amperometric controller allowed levels of 1-2 ng/mL 5MeTHF to be measured in 500 microL of plasma. Daily appraisal of the ratio produced by authentic materials clearly demonstrated that quantitation using dual detection was not subject to problems of differential response. Inter-day variation of the differential detector response is cited. Comparison of the Lactobacillus casei bioassay with HPLC demonstrates good agreement between methods but at the same time highlights the drawback of using such non-specific methods to measure samples where more than one folylmonoglutamate may be present. Antoxidant free storage for three months at -70 degrees C in darkness resulted in no deterioration of 5MeTHF. A comparison of the means and range of values for plasma folate obtained using HPLC, L. casei bioassay and the radiometric binding assay is reported.

Chromatography, High Pressure Liquid↗
PubMed1989

In vivo characterization of the absorption and biotransformation of pteroylmonoglutamic acid in man: a model for future studies.

HPLC-EC has been used to measure the appearance of 5-CH3-H4 folic acid in human plasma following oral administration of folic acid. The process was found to be saturable in accordance with Michaelis-Menten kinetics. The apparent Km for this enzyme system indicates that low doses of oral folic acid are rapidly converted into 5-CH3-H4 folic acid, an observation consistent with the needs of intestinal absorption of essential trace nutrients. The appearance of L. casei active folate in plasma was not rate-limited and showed a biphasic relationship to dose. Preparative HPLC combined with L. casei bioassay demonstrated that most of the L. casei active folate appearing in plasma following a 20,000-micrograms dose of folic acid was due to the unmodified vitamin, only 5.6% being due to 5-CH3-H4 folic acid and with no detectable contribution from 5-CHO-H4 folic acid. The absorption characteristics of the system seem consistent between and within subject(s). No relationship could be demonstrated between predose levels of plasma 5-CH3-H4 folic acid and total folate in erythrocytes, which reflect the status of transport and storage forms of the vitamin, respectively.

Absorption↗
PubMed1989

Biotransformation of pteroylmonoglutamic acid during absorption: implications of Michaelis-Menten kinetics.

Previously reported work from this laboratory has shown that, in man, the formation of plasma 5-methyltetrahydrofolic acid (5MeTHF) from orally administered pteroylmonoglutamic acid (PGA) obeys Michaelis-Menten kinetics. The regression equation obtained from a plot of the reciprocal amount of 5MeTHF formed (micrograms per litre plasma/min) as a function of reciprocal amount of PGA administered (micrograms/kg body weight) provides a useful means of calculating the improved efficiency of 5MeTHF formation by dividing the total dose of PGA into smaller doses.

Adult↗
PubMed1987

Improved high-performance liquid chromatographic procedure for the determination of chlormethiazole levels following solid-phase extraction from plasma.

An improved high-performance liquid chromatographic method for the determination of chlormethiazole levels in plasma is described. The drug is extracted from plasma using commercially available reversed-phase extraction columns; recovery values obtained using Sep-Pak C18 and Bond Elut C1, C2, C4, C6, C8, C18 columns are compared. Separation was achieved by reversed-phase chromatography, using a mobile phase consisting of 0.025 M sodium acetate buffer, pH 4.5-acetonitrile (67:33) at a flow-rate of 1.6 ml/min in conjunction with a 15-cm Jones Chromatography Apex ODS column. The analytical column was protected by a Waters Assoc. Guard-Pak module containing a Guard-Pak CN insert. Using ultraviolet detection at 254 nm chlormethiazole levels in the region of 50 ng/ml can be measured with only 500 microliter of plasma.

Chlormethiazole↗
PubMed1986

High-performance liquid chromatographic determination of carbamazepine and carbamazepine 10,11-epoxide in plasma and saliva following solid-phase sample extraction.

A rapid, sensitive and simple to operate high-performance liquid chromatographic method for the simultaneous determination of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-EP) in plasma and saliva is described. The drug and its metabolite are extracted from both plasma and saliva using commercially available reversed-phase octadecylsilane bonded silica columns (Bond-Elut C18, 2.8 ml capacity). Separation of CBZ and CBZ-EP was achieved by reversed-phase chromatography, using a mobile phase consisting of acetonitrile-methanol-water (19:37:44) at a flow-rate of 1.8 ml/min in conjunction with a Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a Z-module RCSS and protected by a Guard-Pak precolumn module containing a Guard-Pak mu Bondapak C18 insert. Using ultraviolet detection at 214 nm, levels in the region of 50-100 ng/ml for CBZ and CBZ-EP can be measured with only 250 and 500 microliters of plasma and saliva, respectively. The method, which has been used to determine steady-state concentrations of the drug and its metabolite in paediatric patients receiving CBZ monotherapy, is also suitable for pharmacokinetic studies.

Carbamazepine↗
PubMed1986

Solid-phase extraction of acetazolamide from biological fluids and subsequent analysis by high-performance liquid chromatography.

A sensitive, relatively fast and simple to operate high-performance liquid chromatographic method for the determination of acetazolamide in plasma and saliva is described. Quantitative extraction of the drug from both plasma and saliva was achieved using commercially available reversed-phase octadecylsilane-bonded silica column (Bond-Elut C18, 2.8 ml capacity). Acetazolamide and the internal standard are retained on the Bond-Elut C18 column and reproducibly recovered by elution with methanol. Liquid-liquid partition chromatography, carried out on a 30-cm mu Porasil column (10-microns porous silica) using a mobile phase consisting of dichloromethane-ethanol-water-glacial acetic acid (500:65:65:1), provided adequate separation with acceptable retention times. Acetazolamide levels in the region 50-100 ng/ml can be determined in 100 microliters of plasma or 200 microliters of saliva employing ultraviolet detection at 254 nm with a sensitivity of 0.005 absorbance units full scale. Although the method is primarily used to determine steady-state drug levels in paediatric patients, its general applicability is illustrated by the 24-h plasma and saliva concentration profiles obtained from a male volunteer following oral administration of acetazolamide.

Acetazolamide↗
PubMed1986

'Imagine you're clever'.

A series of four studies was conducted to investigate the influence of role enactment on problem-solving in 6-10 yr old children from a disadvantaged background. It was hypothesized that asking the child to enact someone 'clever' (and in one instance someone 'not clever'), would modify the child's performance on the Matching Familiar Figures test as against performance under standard administrative conditions. Apart from the 6 yr old sample, the findings supported the experimental hypothesis. In addition, the speech of 7 and 8 yr old impulsive and reflective children, and children previously administered reflectivity training schemes, was analysed in terms of a classification scheme of reflexivity. No differences were found between these groups on the measures of reflexivity used in speech. The implications of these findings and this approach for disadvantaged children are discussed.

Child↗
PubMed1986

A rapid HPLC method for monitoring plasma levels of caffeine and theophylline using solid phase extraction columns.

A simple HPLC method for the determination of caffeine and theophylline in plasma is described. Separation of theobromine, paraxanthine, theophylline, beta-hydroxyethyltheophylline and caffeine is obtained using a mobile phase of 1% acetic acid/methanol (83:17, v/v) and a Waters Associates NOVA-PAK C18 column protected by a Guard-PAK precolumn module containing a Guard-PAK CN cartridge. Rapid sample preparation is achieved by solid-phase extraction columns (Bond-Elut C18, 1 mL capacity) which provide excellent recovery values for both drugs. The cost per sample using this approach can be minimised by column regeneration and re-use. Results obtained for theophylline are in good agreement with values determined by other techniques.

Caffeine↗
PubMed1985

Improved high-performance liquid chromatographic method for the simultaneous determination of caffeine and its N-demethylated metabolites in plasma using solid-phase extraction.

An improved high-performance liquid chromatographic method for the simultaneous determination of caffeine and its N-demethylated metabolites in plasma is described. Excellent resolution of all components is provided by reversed-phase chromatography using a mobile phase consisting of 1% acetic acid-methanol (83:17) at a flow-rate of 2.7 ml/min, in conjunction with a Waters Assoc. Nova-Pak C18 column which was protected by a Waters Assoc. Guard-Pak precolumn module containing a Guard-Pak CN cartridge. Rapid extraction of caffeine and the dimethylxanthines from plasma was achieved using reversed-phase octadecylsilane bonded-silica columns (Bond-Elut C18). With only 100 microliters of sample, plasma levels in the region of 50 ng/ml for the dimethylxanthines and 100 ng/ml for caffeine can be determined using ultraviolet detection at 273 nm. The method has been used for measuring umbilical cord plasma samples to provide information regarding foetal exposure to caffeine and its metabolites and is also suitable for therapeutic drug monitoring of caffeine and theophylline levels in the treatment of neonatal apnoea.

Caffeine↗