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Biomedical subjects

R O Day

Publications and source records attributed to R O Day.

At least 127 records · Page 7Linked to original sources

Effect of food and various antacids on the absorption of tenoxicam.

1 Twelve healthy volunteers received a single oral dose of tenoxicam 20 mg on six occasions separated by 3 weeks. 2 The six occasions were: fasted overnight; postprandial; fasting and 15 ml aluminium hydroxide gel; postprandial and 15 ml aluminium hydroxide gel; fasting and 15 ml aluminium and magnesium hydroxide gel; postprandial and 15 ml aluminium and magnesium hydroxide gel. 3 Twenty plasma samples were collected over 15 days following dosing with tenoxicam. 4 The following kinetic parameters for plasma tenoxicam were compared: peak concentrations, time taken to reach peak concentrations, area under the plasma concentration-time curve (AUC) and half-life of elimination. 5 Food lengthened the time taken to reach peak tenoxicam concentrations (5.82 +/- 4.6 vs 1.84 +/- 1.0 h in the fasting state; P less than 0.02) and marginally reduced the peak concentrations achieved. AUC was not affected by any of the different regimens. 6 These effects of food on tenoxicam bioavailability are unlikely to be of clinical significance during chronic dosing with the drug.

Adult↗

Classification of overdose/self-poisoning presentations to an accident and emergency department.

A simple classification system of overdoses presenting to a hospital emergency department is described. Five major overdose categories were developed (accidental, suicidal behavior, recreational/experimentation, compulsive use, and an indeterminate category), which were divided into 10 subcategories. A prospective survey at an inner-city hospital in Sydney classified 199 consecutive self-poisoning presentations as being due to compulsive drug use in 38% of cases; suicidal gesture as a reaction to stress, 17%; adverse reactions to recreational or experimental use, 15%; suicidal gesture to influence others, 7%; genuine accident or noncompliance with medication, 6%; genuine suicide attempt, 3%; and pseudo-overdose, 3%. The reason for the overdose was uncertain in the remainder of the cases. Additional data are also presented, including the types of drugs involved in each overdose category. Categories of overdose may be useful in psychosocial assessment for follow-up interventions, assist in research, and help reduce negative attitudes toward overdoses.

Accidents↗

Drugs involved in self-poisoning: verification by toxicological analysis.

During a two-month prospective survey in a metropolitan teaching hospital's accident and emergency department, 239 consecutive drug-related attendances (excluding admissions to hospital that were primarily alcohol related) were identified. This represented 2.6% of total attendances. Of the 199 patients who presented to hospital with self-poisoning, a biological specimen was obtained from 158 (79%) for toxicological analysis, thus providing reliable data on the drugs that were involved in the overdoses. The most common drug groups that were identified were barbiturate (51% of cases) and benzodiazepine (49%) agents, alcohol with other drugs (44%), cannabinoids (32%) and opiate analgesic drugs (25%). Quinalbarbitone and amylobarbitone (Tuinal) and oxazepam were the most common "single" preparations. The use of cannabis and alcohol and the use of several drugs concurrently were more common than in previously reported surveys of self-poisoning. Discrepancies between the purported drug consumption and the toxicological results were frequent; complete agreement occurred in only 35% of the cases. The TOXI-LAB system was an adequate method for toxicological analysis. However, for epidemiological studies an additional back-up method is recommended to verify the presence of some drugs such as barbiturate and benzodiazepine agents.

Alcohol Drinking↗

Comparison of methotrexate with azathioprine or 6-mercaptopurine in refractory rheumatoid arthritis: a life-table analysis.

Methotrexate (MTX) appears to be useful in patients with rheumatoid arthritis (RA) refractory to other drugs but its long-term toxicity and efficacy are uncertain. A retrospective study of MTX in such patients in comparison with the purine analogues, azathioprine and 6-mercaptopurine was made using life-table analysis. Eighty-four patients took MTX in a median dose of 7.5 mg/week whilst 55 received purine analogues, 100 mg/day (median). By 12 months, 19.3% of patients had ceased MTX due to toxicity, compared with 29.3% for purine analogues. Toxicity severe enough to warrant stopping therapy was uncommon after 8 months with either drug. At 12 months 61.5% of the MTX patients had achieved defined criteria of improvement compared with 25.6% for the purine analogues (p less than 0.05). The number of patients improving on purine analogues did not increase substantially after 6 months, whereas the number improving with MTX continued to 12 months. MTX in a low-dose regimen is useful in refractory RA and superior to low-dose purine analogues.

Actuarial Analysis↗

Interactions between non-steroidal anti-inflammatory drugs and antihypertensives and diuretics.

Non-steroidal anti-inflammatory drugs (NSAIDs) may increase blood pressure and antagonise the effects of antihypertensive agents. They can cause salt and water retention and an increase in extracellular volume. NSAIDs also cause a decrease in prostaglandin synthesis in blood vessel walls which removes a direct vasodilatory influence and also increases the vascular response to vasoconstrictor stimuli. The hypotensive effects of frusemide and captopril are due in part to their stimulation of prostaglandin synthesis. Hence the antagonism of the hypotensive effect of these agents is probably due to NSAID-induced inhibition of prostaglandin synthesis. However, the interactions of NSAIDs with the other antihypertensive agents may not be related to inhibition of antihypertensive-induced release of prostaglandin but to independent and opposing actions of the NSAIDs on the various physiological mechanisms which regulate blood pressure. Clinicians should remain alert to these potential drug interactions.

Anti-Inflammatory Agents, Non-Steroidal↗

Aurothioglucose in rheumatoid arthritis. Outcome of treatment in patients intolerant of sodium aurothiomalate.

Forty-three patients in whom treatment with sodium aurothiomalate was discontinued because of adverse reactions that either were relatively severe or recurred on rechallenge received treatment with aurothioglucose in oily base. Thirty-six of them had rheumatoid arthritis, four had psoriatic arthritis and three had juvenile chronic arthritis. Aurothioglucose therapy was introduced cautiously and increased gradually to a maintenance regimen, usually 5-20 mg/week, administered by intramuscular injection. The clinical response was good in 25 patients (60%), 14 of whom continued to receive aurothioglucose therapy on a long-term basis. Adverse reactions to aurothioglucose developed in 17 patients (40%); these were generally mild, and, in all but four patients, were of the same type as those induced by sodium aurothiomalate therapy. Results show that aurothioglucose in oily base may be successfully administered in a low-dose regimen to selected patients who are intolerant of sodium aurothiomalate.

Arthritis, Rheumatoid↗

Liquid chromatographic determination and plasma concentration profile of optical isomers of ibuprofen in humans.

A sensitive and specific high-performance liquid chromatographic assay for the optical isomers of ibuprofen in plasma is reported. The isomers were converted to their diastereoisomeric S(+)-2-octyl esters and were resolved with two silica columns in series and a mobile phase containing 0.05% isopropyl alcohol in heptane. The lower limit of sensitivity was 0.5 micrograms/mL. The plasma concentrations of the optical isomers in a normal volunteer following administration of racemic, S(+)-, and R(-)-ibuprofen are reported. Following administration of R(-)-ibuprofen, there was stereoselective inversion of R(-)- to S(+)-ibuprofen.

Chromatography, High Pressure Liquid↗

High-performance liquid chromatographic analysis of diflunisal in plasma and urine: application to pharmacokinetic studies in two normal volunteers.

A high-performance liquid chromatographic (HPLC) assay with fluorescence detection has been developed for the determination of diflunisal in plasma and urine. The plasma or urine, containing naproxen as the internal standard, was extracted with ether-hexane (1:1). The samples were analyzed on a microparticulate column, and the compounds were eluted using a mobile phase of 0.05 M phosphate buffer (pH 3) and methanol. Plasma samples were analyzed from two healthy male subjects who received a 250- and 750-mg oral dose of diflunisal 3 weeks apart. The data were analyzed according to a two-compartment open model. There was a disproportionate increase in the area under the plasma concentration-time curves (AUC 750 mg/AUC 250 mg was 3.84 for subject A and 4.22 for subject B) and a reduction in plasma clearance after the 750-mg dose of diflunisal. These data suggest that the kinetics of diflunisal may be dose dependent.

Chromatography, High Pressure Liquid↗

Relationship of serum naproxen concentration to efficacy in rheumatoid arthritis.

Twenty-four patients with rheumatoid arthritis were tested in a randomized, double-blind. Latin-square comparison of 250, 750 and 1500 mg of naproxen daily. Each received each dose for 2 wk and baseline disease activity was established during withdrawal of medication before and after the study. Nine standard measures of efficacy were tested at each evaluation. No order effect or change in baseline was found. Total and unbound naproxen concentrations were measured by high-pressure liquid chromatography and equilibrium dialysis, respectively. A linear dose-response relationship (P less than 0.05) was demonstrated between naproxen and joint count, patient's pain assessment, activities of daily living index, physician's global assessment, and grip strength. The relationship to patients' global assessment was of uncertain significance (P less than 0.07). A positive dose to serum level correlation (1, 2, and 12 hr after dose) was apparent (r greater than 0.78). When patients were defined as responders or nonresponders by a summed efficacy score, there was a serum concentration-response relationship; the percentage of responding patients increased with each serum level quartile: 25%, 31%, 59%, and 75%. Patients with a trough total serum naproxen concentration under 18 micrograms/ml did not respond, while 76% of patients with trough total serum concentrations above 50 micrograms/ml responded. No serum naproxen toxicity level relationship was established.

Adult↗

Enhanced metabolism of mexiletine after phenytoin administration.

1 Unexpectedly low plasma concentrations of mexiletine were observed in three patients treated with mexiletine and concurrently taking phenytoin. 2 Six healthy volunteers were given a single oral dose of mexiletine (400 mg), before and after 1 week of phenytoin administration (300 mg/day). 3 The mean +/- s.d. area under the plasma mexiletine concentration-time curve decreased from 17.67 +/- 6.21 to 8.01 +/- 3.64 micrograms ml-1 h (P less than 0.003). 4 The mean +/- s.d. half-life of elimination of mexiletine decreased from 17.2 +/- 5.26 to 8.4 +/- 4.17 h (P less than 0.02) 5 The suggested mechanism of the interaction is hepatic mixed-function oxidase enzyme induction by phenytoin. 6 The interaction is likely to be clinically significant.

Adult↗

Antimalarials in rheumatic diseases.

The use of antimalarials in rheumatoid arthritis (RA) and systemic lupus erythematosis (SLE) has declined over recent years due to concern over retinal toxicity and the impression that this class of drugs is relatively ineffective in rheumatic diseases. Recent reviews suggest that this position should be changed. Firstly, there is now good evidence for the efficacy of these drugs in RA and secondly strict control of the daily dosage and careful ophthalmological surveillance can almost eliminate the risk of serious retinal toxicity.

Antimalarials↗