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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 181 records · Page 10Linked to original sources
PubMed1982

Plasma disopyramide concentrations following a 300-mg oral loading dose in acute myocardial infarction.

Plasma disopyramide concentrations were measured in 19 patients with suspected myocardial infarction (MI) following an oral loading dose of 300 mg. Infarction was confirmed in 17 patients. In 10 patients blood samples were collected frequently over a period of 6 h, and in the remaining nine, blood samples were collected for 60 h whilst they were receiving a maintenance dose of 100 mg six hourly. There was a wide variation in the absorption of the drug, and only 8 patients achieved plasma concentrations in the range 2-4 mg/L within one hour of ingestion; 8 of the patients on maintenance therapy were within this range 24 h following the start of therapy. Although only 2 noninfarct patients were observed, they achieved the highest plasma disopyramide concentrations--above the therapeutic range--within 1 h of receiving the loading dose. Narcotic analgesia was associated with poor absorption of the drug, but this does not exclude severity of infarction or vomiting after the loading dose from contributing to the wide variation in plasma concentrations in the early stages following the loading dose. It is concluded that this regime is unsuitable for prophylactic use in acute MI.

Adult↗
PubMed1982

High-performance liquid chromatographic measurement of amiodarone and its desethyl metabolite: methodology and preliminary observations.

A high-performance liquid chromatographic technique is described for the measurement of amiodarone and its desethyl metabolite in plasma. Preliminary observations are presented on the concentrations of metabolite found during the early stages of chronic amiodarone therapy. A case history is outlined in which noncompliance during treatment with amiodarone was confirmed by measurement of the ratio of desethylamiodarone to amiodarone concentrations.

Amiodarone↗
PubMed1982

Identification and measurement of desethylamiodarone in blood plasma specimens from amiodarone-treated patients.

Desethylamiodarone has been identified as the principal lipophilic metabolite of amiodarone present in plasma specimens from amiodarone-treated patients. This structure has been confirmed by probe-injection mass spectrometry of column effluent fractions and comparison with the authentic compound using both chromatographic and mass spectrometric techniques. Although there is no information available as to the pharmacological activity of desethylamiodarone in man, the plasma concentrations of this metabolite attained during chronic amiodarone therapy are similar to those of the parent compound (0.1-4 mg litre-1).

Amiodarone↗
PubMed1982

A trial of prophylactic mexiletine in home coronary care.

A double blind randomised study was undertaken comparing the effects of oral mexiletine and placebo given by general practitioners at home in the early stages of suspected acute myocardial infarction, and continued for six weeks. The study comprised 216 patients. In 59 the diagnosis of acute myocardial infarction was not confirmed. Of the 72 patients with confirmed myocardial infarction treated with mexiletine, 11 (15.3%) died, compared with 19 (22.4%) of the 85 patients given the placebo, and significantly fewer of the former compared with the latter had frequent ventricular ectopics or ventricular tachycardia recorded on 24 hour electrocardiograms. Numbers of patients transferred to hospital or withdrawn from the trial because of arrhythmia or heart failure were similar in the two treated groups. Ten (13.9%) of the patients taking mexiletine had the drug withdrawn because of side effects attributed to it, compared with three (3.5%) of the group taking the placebo. A further five patients (all on mexiletine) also had treatment withdrawn because of side effects but infarction was not later confirmed. The results indicate that oral mexiletine can be given safely to patients with suspected myocardial infarction at home by their general practitioners in the absence of a positive electrocardiographic diagnosis. The frequency of ventricular tachycardia is significantly reduced; but there is no evidence of reduced mortality.

Aged↗
PubMed1981

Rapid high-performance liquid chromatographic method for the measurement of verapamil and norverapamil in blood plasma or serum.

A simple high-performance liquid chromatographic method for the simultaneous measurement of plasma verapamil and norverapamil concentrations has been developed. The sample (100 microliters) is vortex-mixed for 30 sec with 4 M sodium hydroxide solution, pH 13 (50 microliters), internal standard solution (aqueous 5,6-benzoquinoline, 0.20 mg/l) (50 microliters) and methyl tert.-butyl ether (200 microliters). After centrifugation at 9950 x g for 2 min, a portion (100 microliters) of the resulting extract is analysed on a microparticulate (5 microns) silica column using a methanolic solution of potassium bromide (3.0 mM) and perchloric acid (0.37 mM) as the mobile phase, and the column effluent is monitored by fluorescence detection using an excitation wavelength of 203 nm. A specimen, together with a quality control sample, can be analysed, in duplicate, within 30 min. The limit of accurate measurement of the assay is 2 micrograms/l, and no potential sources of interference have been identified. The method has advantages of speed, small sample requirement and complete resolution of the three major metabolites of verapamil.

Chromatography, High Pressure Liquid↗
PubMed1980

Rapid high-performance liquid chromatographic method for the measurement of amiodarone in blood plasma or serum at the concentrations attained during therapy.

A simple high-performance liquid chromatographic method has been developed for the measurement of the antiarrhythmic drug amiodarone in small (200 microliter) volumes of plasma or serum. After addition of 2 mole/l phosphate solution, pH 4.5 (20 microliter), containing the internal standard, the sample is vortex-mixed with diisopropyl ether (200 microliter) for 30 sec. A portion (100 microliter) of the resulting extract is analysed on a microparticulate (5 micron) silica column using methanol-diethyl ether (85:15) containing perchloric acid (0.02% v/v) as the mobile phase, and the absorption of the column effluent is monitored at 240 nm. No endogenous sources of interference have been observed, and interference from other drugs is minimal. The procedure is rapid, an analysis in duplicate taking less than 15 min to complete. The limit of sensitivity of the assay is 0.05 mg/l, and the concentrations of amiodarone measured in plasma samples from patients under treatment with this compound ranged from 0.15 to 4.5 mg/l.

Amiodarone↗
PubMed1980

Successful management of serious disopyramide poisoning.

A case of deliberate disopyramide overdosage is described. Circulatory collapse was treated by means of a large dose of isoprenaline, and charcoal haemoperfusion was used in an attempt to enhance the elimination of disopyramide. The suitability of this treatment regime is discussed in the light of findings from animal studies and the implications for the management of the disopyramide-poisoned patient are considered.

Adult↗
PubMed1980

Electrophysiological properties of mexiletine assessed with respect to plasma concentrations.

Electrophysiological measurements were made before and after the intravenous administration of mexiletine in 14 patients with preexcitation syndromes. Following a single infusion of 3 mg/kg body weight plasma concentrations of mexiletine fell rapidly and after 15 min, significant changes in electrophysiological measurements were not found. Higher plasma mexiletine concentrations, bringing about a pharmacological effect, were attained when a second intravenous infusion was also given. The results suggest a minimum effective plasma concentration for mexiletine of about 0.5 mg/l. Side-effects were minimal and their production was largely dependent on the rate of drug infusion. Electrophysiological measurements in previous studies may have been made at a time when plasma mexiletine concentrations were below an effective level and this could explain a disparity in their findings.

Adolescent↗
PubMed1979

Simple gas-liquid chromatographic method for the measurement of mexiletine and lignocaine in blood-plasma or serum.

A simple method has been developed for the measurement of mexiletine and lignocaine in blood-plasma or serum at the concentrations attained during therapy. A relatively small (200 microliter) sample volume is made basic and extracted with 50 microliter of chloroform containing internal standards, and the extract is analysed directly by gas-liquid chromatography with flame-ionisation detection on two separate columns. The instrument calibrations are linear and pass through the origin of the graphs. Neither solvent transfer nor evaporation steps are used in the extraction procedure, which takes less than 3 min to complete, and no interference from either endogenous sample constituents or other drugs has been observed.

Chromatography, Gas↗