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Biomedical subjects

R W Bury

Publications and source records attributed to R W Bury.

At least 37 records · Page 2Linked to original sources
PubMed1987

Changes in clearance of sodium valproate with changes in dose.

The relationship between total sodium valproate concentrations and drug clearance was studied in four patients, by the evaluation of clearance at two different doses. In each patient, the average unbound fraction for a dosing interval increased with increase in sodium valproate dose. Despite this increase in unbound fraction, there was no increase in total drug clearance, and in each patient there was a decrease in clearance of the unbound drug. These findings suggest either that the drug is restrictively cleared and there is a dose-related decline in intrinsic clearance, or, contrary to previous reports, that sodium valproate is cleared nonrestrictively.

Adult↗
PubMed1985

Effect of impairment of renal function on the accumulation and disposition of isoxicam.

The accumulation and disposition of the non-steroidal antiinflammatory drug isoxicam were investigated following its oral administration to 6 subjects with normal renal function and 13 patients with diminished renal function. Isoxicam was given daily as a single oral dose for 14-15 consecutive days. Steady-state plasma levels were achieved after 13 days. The effect of differences in renal function on the kinetics of isoxicam appeared to be minimal. Accumulation of isoxicam was similar in both groups of subjects and there was no significant difference between the groups in the plasma clearance or terminal half-life of isoxicam. There were substantial differences between individuals in the apparent plasma clearance and half-life of the drug, and this is reflected in the 7-fold range of steady-state plasma isoxicam concentrations encountered in the subjects.

Adult↗
PubMed1984

Disposition of intravenous glycofurol: effect of hepatic cirrhosis.

The disposition of intravenous glycofurol, a solvent for some drugs, was followed in nine male patients with hepatic cirrhosis. In comparison with age-matched controls, glycofurol clearance in the patients with cirrhosis was reduced 43% and terminal t 1/2 was prolonged 103%. There was no significant difference between the cirrhotic and control groups in volume of distribution.

Half-Life↗
PubMed1983

Acute phenylbutazone poisoning in a child.

Accidental acute intoxication with phenylbutazone in a 2 1/2-year-old child produced an acute picture of coma, convulsions, diarrhoea, and of cholestatic jaundice which evolved over the succeeding 10 days. Transient, unexplained hyperglycaemia occurred during the first few hours of the illness. Recovery was complete within three weeks after the poisoning. Her clinical progress was monitored with the aid of regular estimations of plasma phenylbutazone levels.

Acute Disease↗
PubMed1983

The effect of ethanol administration on the disposition and elimination of chlormethiazole.

Acutely administered ethanol has been shown to inhibit the hepatic metabolism of a number of drugs. Ethanol might be expected to decrease the first-pass extraction of chlormethiazole leading to higher blood levels of this high clearance sedative frequently used in the management of alcoholic patients. Chlormethiazole has a narrow therapeutic index and the unexpected deaths reported in alcoholics taking this drug may have been due to an effect of ethanol on the metabolism of chlormethiazole. However in this study, acutely administered ethanol maintained at levels around 22 mmol/l had no significant effect on the disposition or elimination of either daily or intravenously administered chlormethiazole.

Administration, Oral↗
PubMed1983

Elimination of amphotericin B in impaired renal function.

The influence of impaired renal function on the steady-state plasma clearance of amphotericin B was determined in seven patients with creatinine clearances ranging from zero to normal. Contrary to previous reports, steady-state plasma concentrations of total drug were lower in uremic patients than in patients with normal renal function. Total plasma clearance of amphotericin B ranged from 16.7 to 39.9 ml/min, correlated directly with the plasma creatinine concentration, and correlated inversely with the creatinine clearance. Urinary excretion of unchanged drug accounted for less than 10% of the dose. In 10 healthy subjects, mean percent of amphotericin B unbound in plasma was 3.55 +/- 0.32 (SD). Binding was determined in a further group of 10 uremic patients. Mean unbound percent (4.15 +/- 0.73, SD) was higher than in the healthy subjects, and the binding ratio (molar concentration of bound to unbound drug) correlated weakly with the creatinine clearance. This suggests that plasma clearance of unbound amphotericin B and, therefore, steady-state plasma concentrations of unbound drug are not affected by renal impairment, and that dosage requirements will be overestimated if based on measurements of total drug plasma concentration.

Adult↗
PubMed1983

Absorption of orally administered amphotericin B lozenges.

The systemic absorption of amphotericin B, administered as a 10 mg lozenge, was investigated in 14 patients with malignancies, who received three or four doses daily during chronic administration. The mean plasma amphotericin B concentration, measured 3 h after the morning dose on from 1-20 occasions over a 1-80 day period, ranged among subjects from 46 +/- 13 ng/ml (s.d., n = 20) to 136 +/- 25 ng/ml (n = 19). Using the previously reported intravenous clearance of the drug, the fraction of the dose absorbed was estimated at 8.3-9.9%. This is considerably greater than that estimated from earlier reports (0.2-0.9%), which used much higher oral doses (2-10 g/day).

Absorption↗
PubMed1982

Mexiletine vs. lignocaine in the management of ventricular arrhythmias after open-heart surgery.

We made an open comparison of lignocaine and mexiletine in the treatment of ventricular arrhythmias occurring after open-heart surgery. Thirty patients whose arrhythmia did not respond to correction of metabolic disturbances were randomly allocated to receive treatment either with lignocaine or with mexiletine in fixed dosage schedules (15 in each group). Failure to control the rhythm or recurrent abnormality led to administration of a further dose and, if this was unsuccessful, to crossover to the alternative agent. The two drugs were comparable in efficacy, but mexiletine was slightly more effective when administered after lignocaine than the converse.

Arrhythmias, Cardiac↗
PubMed1982

Paracetamol self-poisoning: diagnosis, management, and outcome.

Over a four-year period, 103 patients presented to St Vincent's Hospital, Melbourne, after poisoning themselves with paracetamol. Most of them were young adults who suffered temporary emotional or social distress. There was severe liver damage in four patients who presented, or were recognised, 24 hours or more after the ingestion of paracetamol. The absence of severe liver damage in the remaining 99 patients was attributed to early intervention with specific therapy with orally administered methionine or intravenously administered N-acetylcysteine. We describe a rapid plasma paracetamol assay which can aid in the diagnosis and management of this problem. All physicians should be aware that paracetamol-induced hepatic necrosis is not clinically apparent for two to three days, and that it can be prevented by early specific treatment.

Acetaminophen↗
PubMed1981

Use of a drug-screening service in an inner-city teaching hospital.

Experience in urinary drug screening at St Vincent's Hospital, Melbourne, was evaluated over a period of 12 months after the introduction of a commercially available thin-layer chromatographic system which expanded the capabilities and improved the efficiency of the service. Specimens from 167 patients were screened when either drug overdose, or drug abuse, or poor compliance with prescribed medications was suspected. Screening was also undertaken to aid solution of diagnostic problems by excluding the possibility of drug ingestion. Benzodiazepines, barbiturates, and tricyclic antidepressants represented the drug groups which were most frequently detected. Multiple drug use was common with the mode and median number of drugs taken being two. For 75% of the patients studied, relevant information about drug intake was either unreliable or not obtainable before drug screening. Retrospective examination of the case histories showed that drug screening assisted in arriving at diagnostic or management decisions for at least 66% of the patients.

Adolescent↗
PubMed1981

Cimetidine impairs the elimination of chlormethiazole.

Cimetidine impairs the systemic clearance of a number of low extraction drugs and this study examines its effect on the oral clearance of the high extraction drug, chlormethiazole. Cimetidine (1 g/day for 7 days) caused the clearance of chlormethiazole to fall to 69% of pretreatment values. It also prolonged the elimination half-life by 60%. The findings indicate that the metabolism of chlormethiazole is inhibited by cimetidine and the co-administration of these drugs may lead to excess sedation and respiratory depression.

Adult↗