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Biomedical subjects

B G Charles

Publications and source records attributed to B G Charles.

At least 55 records · Page 3Linked to original sources
PubMed1994

Determination of dexamethasone in plasma of premature neonates using high-performance liquid chromatography.

A high-performance liquid chromatographic assay is described for dexamethasone in neonatal plasma. Samples (100 microliters) were extracted with ethyl acetate (1.0 ml) containing 50 ng of beclomethasone. The mobile phase of acetonitrile-0.01 M phosphate buffer (pH 7.0) (45:55, v/v) was pumped at a flow-rate of 1.0 ml/min through an Ultrasphere ODS column (5.0 microns particles). Detection was by UV absorbance at 240 nm. Calibration plots were linear (r2 > 0.999) from 10-1000 ng/ml. Within-day and between-day precision (C.V.%, coefficient of variation) between 15-900 ng/ml was 1.21-20.6%. Inaccuracy was 7.7%, or less. The minimum quantifiable concentration (C.V. approximately 20%) was 15 ng/ml. Recovery (20-1000 ng/ml) exceeded 75%. Concomitant neonatal medication did not interfere.

Chromatography, High Pressure Liquid↗
PubMed1994

Comparative in vitro and in vivo bioavailability of naproxen from tablet and caplet formulations.

A 500 mg dose of naproxen in a caplet formulation (product A) or a tablet (Naprosyn 500, product B) was administered to 14 fasting healthy subjects on two separate occasions, separated by a 1-2 week washout period in an open, randomized crossover. Blood samples were drawn periodically and plasma naproxen concentrations measured by HPLC. The median time Tmax to reach peak concentration for product A was shorter than that for product B (1.025 h versus 1.5 h) but A and B were similar with respect to median peak plasma concentration Cmax (77.9 mg l-1 versus 71.4 mg l-1), and average area AUC0-infinity under the plasma concentration-time curve (1210.2 mg l-1 h versus 1211.0 mg l-1 h). In vitro parameters (A versus B) of mean dissolution time MDT (5.03 min versus 15.0 min), and time for 70% dissolution T70 (6.67 min versus 20.2 min), differed significantly.

Adolescent↗
PubMed1994

A retrospective study of risk factors of akathisia in terminally ill patients.

Akathisia is a distressing disorder that manifests as a state of restlessness and motor agitation. We aim to highlight the problem of akathisia to the palliative care physician by identifying and quantifying risk factors in the terminally ill. A retrospective case-control study was utilized to investigate risk factors for akathisia. Medical records of cases (N = 100) and controls (N = 365) archived in a computerized database were downloaded and risk factors determined using conditional logistic regression analyses. Exposure to pharmacologically similar drugs, such as haloperidol [odds ratio (OR), 18.4; 95% confidence interval (CI), 8.2-41.4], prochlorperazine (OR, 8.1; 95% CI, 3.0-21.8), and promethazine (OR, 3.3; 95% CI, 1.3-8.0), conferred an increased risk. Other significant variables were exposure to morphine (OR, 5.3; 95% CI, 1.9-14.2), sodium valproate (OR, 2.5; 95% CI, 1.0-6.4), and sodium bicarbonate/tartrate (Ural) (OR, 4.2; 95% CI, 1.2-15.3). Highlighting factors that predispose patients to akathisia emphasizes that this syndrome should not be forgotten when treating the terminally ill. It is recommended that those drugs identified should be judicially used and carefully monitored.

Adult↗
PubMed1994

Gentamicin dosing in elderly patients based on bioelectrical impedance analysis.

The relationship between gentamicin pharmacokinetics and measures of bioelectrical impedance (BI) in elderly patients was investigated with the aim of developing a potential noninvasive means of individualising gentamicin dosage. Linear regression analyses identified height/resistance2 as a statistically significant predictor of gentamicin distribution volume, V, [adjusted (adj)r2 = 0.53, coefficient of variation (CV) = 15.2%], and resistance/reactance and creatinine clearance (CLcr) as predictors of total systemic clearance, CL, adj r2 = 0.52, CV = 20.1%. Individualisation of gentamicin dosage regimens based on these relationships to achieve steady-state (SS), peak gentamicin concentrations, Css,max, and SS trough concentrations, Css,min, of 7.0 and 1.0 micrograms/ml, respectively, in an independent group of elderly patients resulted in serum gentamicin levels of 5.9 +/- 0.7 and 0.8 +/- 0.4 micrograms/ml. Mean absolute prediction errors averaged 0.7 +/- 0.5 micrograms/ml for Css,max and 0.5 +/- 0.3 micrograms/ml for Css,min. Measures of BI provided the best predictions of Css,max, whereas models based on CLcr alone were the best predictors of Css,min. This technique provides a means of complementing routine pharmacokinetic monitoring of gentamicin pharmacotherapy in the elderly hospitalised patient with reductions in patient discomfort and potential savings in time and cost.

Aged↗
PubMed1994

Determination of dose-dependent absorption of amoxycillin from urinary excretion data in healthy subjects.

Measurement of unchanged drug in urine was used to study the rate and extent of amoxycillin absorption after administration of amoxycillin sodium solution to six healthy subjects in a Latin-Square crossover design. The mean (95% CI) fraction of the dose excreted as unchanged amoxycillin decreased (P < 0.05) from 0.50 (0.44-0.56) after 97 mg amoxycillin sodium (= 0.25 mmol amoxycillin) to 0.23 (0.19-0.27) after 3103 mg (8 mmol), while the mean residence time determined from urinary excretion rate data increased (P < 0.05) from 1.54 (1.32-1.76) h to 2.16 (2.01-2.41) h. Plots of total urinary excretion and initial (0-30 min) excretion of unchanged drug vs dose indicated significant non-linearity above 776 mg doses. Michaelis-Menten parameters describing this relationship with respect to amount absorbed were 3.02 mmol for maximum amount absorbed and 1.93 mmol for amount absorbed at half maximum for 0-30 min. These results support a saturable absorption mechanism for amoxycillin which had clinical implications for high oral amoxycillin doses, and for competition with other drugs having capacity-limited absorption.

Adult↗
PubMed1993

High-performance liquid chromatographic determination of amoxicillin in urine using solid-phase, ion-pair extraction and ultraviolet detection.

A simple, robust high-performance liquid chromatographic method is described for assaying amoxicillin in urine. Sample clean-up involved solid-phase, ion-pair extraction onto Sep-Pak C18 cartridges followed by elution with acetonitrile (3%, v/v) in pH 4.85 buffer. Separations were performed on an Ultrasphere C18 column with a mobile phase comprising acetonitrile (32.5 ml) and pH 7.1 phosphate buffer (0.01 M, 1000 ml). Peaks were detected at 229 nm. Recovery was greater than 94%. Plots of peak area against urinary amoxicillin concentration were linear (r > 0.999) from 5 to 500 mg/l. Between-day and within-day imprecision (coefficient of variation) ranged between 3.0 and 15.5%. Inaccuracy was 7.1%, or less.

Amoxicillin↗
PubMed1993

Simple microscale high-performance liquid chromatographic method for determination of furosemide in neonatal plasma.

A simple microscale high-performance liquid chromatographic method using fluorescence detection for the quantitation of furosemide in neonatal plasma is described. Sample pre-treatment involved protein precipitation of 25 microliters of plasma with 100 microliters of acetonitrile. The mobile phase consisted of acetonitrile (460 ml) and 0.08 M orthophosphoric acid (540 ml) and was delivered at 1.1 ml/min. Calibration curves were linear from 0.1 to 25 micrograms/ml. Within-day and between-day imprecision (coefficient of variation) was 3.9-6.1, and 6.1-12.2%, respectively. Furosemide was eluted after 6.5 min and naproxen (internal standard) after 11.5 min. The assay was validated for application in neonatal plasma containing a wide range of albumin concentrations.

Chromatography, High Pressure Liquid↗
PubMed1993

Assessment of bioelectrical impedance for individualizing gentamicin therapy in neonates.

The use of bioelectrical impedance (BI) analysis as a non-invasive approach for individualizing gentamicin therapy in newborn infants has been investigated in a two phase study. In Phase I, 1/impedance and length were identified as statistically significant predictors of the distribution volume of gentamicin (Adj R2 = 0.78, CV = 12.42%), and length/impedance and post-conceptual age were predictors of total systemic clearance (Adj R2 = 0.83, CV = 14.5%), following the administration of 2.5 mg.kg-1 gentamicin to 17 neonates (gestational age (GA) 27 to 36 weeks). In a prospective validation of these relationships in an independent (Phase II) group of 27 infants (GA 26 to 41 weeks), predicted serum gentamicin concentrations were close to those achieved. Several instances of high prediction errors (predicted minus achieved levels) were observed in infants with known or suspected renal impairment and they caused significant (P < 0.05) perturbation in the bias and accuracy of the models. Daily BI measures over a four to five day period were able to detect individual changes in the fat-free body compartments, which were translated into alterations in gentamicin regimens. This simple, non-invasive and relatively inexpensive bedside technique provides a potentially valuable means to individualize gentamicin therapy without relying on the measurement of serum gentamicin concentration.

Electric Impedance↗
PubMed1993

Individual theophylline dosing based on bioelectrical impedance analysis.

The role of bioelectrical impedance (BI) analysis in determining slow-release theophylline dosage was evaluated in fifteen healthy subjects given a standard 200 mg dose. Reactance and l/resistance were identified as the most significant predictors of pre-dose, steady-state theophylline concentrations (Css,pre). Compared with doses based on body weight (8.8 mg kg-1 day-1), theophylline doses determined by BI analysis (9.6 +/- 2.4 mg kg-1 day-1) resulted in less biased (mean prediction error = 0.6 vs 1.4) though slightly less precise (mean squared error = 7.1 vs 6.3) Css,pre values. These differences were statistically insignificant (P > 0.05).

Adolescent↗
PubMed1993

Pharmacokinetics and absolute bioavailability of cyclosporin following intravenous and abomasal administration to sheep.

Cyclosporin A pharmacokinetics were studied following intravenous and abomasal dosing in an open, crossover study in healthy, merino ewes. Five different doses of cyclosporin A were dispersed in milk and administered into the abomasum through a surgically inserted fistula which simulates oral administration. Cyclosporin A was well tolerated. Whole blood concentrations of cyclosporin A were measured by HPLC and mean clearance (0.45 +/- 0.05 L h-1 kg-1), distribution volume (4.4 +/- 2.0 L kg-1), mean residence time (9.6 +/- 4.1 h) and half-life (12.1 +/- 3.1 h) were calculated cyclosporin A was excreted in urine or bile. Area under the curve increased proportionally with doses up to 26.3 mg kg-1, but was curvilinear above this dose. Abomasal bioavailability at 6.4 mg kg-1 was 0.26 +/- 0.09, and mean absorption time was 4.7 +/- 11.1 h. Considerable pharmacokinetic variability was observed, particularly after abomasal administration. Cyclosporin A pharmacokinetics in sheep lie within the values reported in man after renal, bone marrow and cardiac transplantation.

Abomasum↗
PubMed1992

Measurement of dothiepin and its major metabolites in plasma by high-performance liquid chromatography.

This paper describes a reversed-phase high-performance liquid chromatographic method which will simultaneously measure dothiepin and its three major metabolites (northiaden, northiaden-S-oxide and dothiepin-S-oxide) in plasma using trimipramine as internal standard. Sample preparation involved a basic extraction using diethyl ether followed by an acid back-extraction. The method we report is linear over the range 50-1000 ng/ml (r = 0.999), for all analytes. Total imprecision is less than 11% (coefficient of variation) and accuracy is greater than 94% (n = 20). Recovery of analytes varied considerably from 51.7% for northiaden-S-oxide to 90.2% for dothiepin-S-oxide.

Chromatography, High Pressure Liquid↗
PubMed1988

A modified assay for cyclosporin in blood using solid-phase extraction with high-performance liquid chromatography.

A modified procedure for measuring cyclosporin in whole blood by high-performance liquid chromatography is described and evaluated for clinical use. Sample preparation uses solid-phase extraction cartridges that can be reused. Life of the reverse-phase analytical column exceeds 1,000 injections at 70 degrees C. Cyclosporins A and D (internal standard) elute after 5.6 and 7.6 min, respectively. Calibration plots are linear from 50 ng/ml to at least 2,000 ng/ml. Within-day and between-day imprecision is less than 9% (coefficient of variation). Minimum measurable concentration is 50 ng/ml.

Chromatography, High Pressure Liquid↗
PubMed1987

Temelastine does not affect theophylline pharmacokinetics in normal subjects.

The pharmacokinetics of theophylline (i.v. aminophylline 250 mg) were studied in a balanced, double-blind crossover following the administration of oral temelastine (100 mg) or placebo, twice daily for 7 days, to 10 normal volunteers. Comparison of volumes of distribution, elimination rate constants, elimination half-lives and areas under the plasma concentration-time curve indicated that temelastine had no significant effect on theophylline pharmacokinetics.

Adult↗
PubMed1984

Rapid HPLC analysis of cefoxitin in plasma and urine.

A rapid, specific and precise method is described for the analysis of cefoxitin in plasma and urine by reversed-phase, high performance liquid chromatography (HPLC). Cefoxitin and the internal standard, 3-isobutyl-l-methyl xanthine are eluted after 5.3 and 7.5 min, respectively. The assay sensitivity limit is 1 to 2 mg/l of cefoxitin sodium at 254 nm. Commonly prescribed antibiotics do not interfere. The assay is suitable for routine monitoring and pharmacokinetic studies of cefoxitin.

Cefoxitin↗