The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29% higher and CL/f was 22% lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, lambda z, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.

Adult↗

PubMed1991

Intentional self-poisoning with glyphosate-containing herbicides.

Four cases of self-poisoning with 'Roundup' herbicide are described, one of them fatal. One of the survivors had a protracted hospital stay and considerable clinical and laboratory detail is presented. Serious self-poisoning is associated with massive gastrointestinal fluid loss and renal failure. The management of such cases and the role of surfactant toxicity are discussed.

Adolescent↗

PubMed1990

Mianserin and agranulocytosis in New Zealand.

The frequency with which agranulocytosis was associated with mianserin in New Zealand was calculated, by two methods, from spontaneous reports to the Intensive Medicines Monitoring Programme (IMMP)--one gave a frequency of 1 in 1354 (95% CI 1 in 3145 to 1 in 685) and the other gave a rate of 1 in 1743 (95% CI 1 in 2895 to 1 in 1116). There were 3 deaths. Age and dose seemed to be related to occurrence of agranulocytosis. The frequency of the complication seemed to be higher than that reported for other countries, perhaps because higher doses were prescribed in New Zealand but also perhaps because of a selection bias in surveys elsewhere. The occurrence of agranulocytosis with mianserin in New Zealand is higher than that of white-cell dyscrasias reported with use of chloramphenicol, phenylbutazone, and oxyphenbutazone, and although the case-fatality rate of agranulocytosis is lower with mianserin than with the other drugs, the overall mortality rate may be higher.

Adult↗

PubMed1990

Quality criteria for early signals of possible adverse drug reactions.

The main function of the World Health Organisation's International Collaborative Programme on Drug Monitoring is to provide a reliable early warning of possible health hazards caused by medicines. Described here is an attempt to devise criteria that would produce a well-founded early signal of an adverse reaction on the basis of reports sent in by national collaborating centres and combined in the WHO database. To reduce the frequency of spurious associations (false-positive signals) it is suggested that publication be delayed until a few case-histories meeting the suggested criteria have been sent in. The criteria were tested retrospectively against early published case-reports on drug-associated agranulocytosis. 19 suspected associations were examined and a signal in the database was defined by there being three or more cases containing stipulated information about the patient and the treatment. The WHO database had reports on all the associations, suggested criteria for a signal being met in 15 instances. This signal was present when the first case was published in 7 instances and within three months of first publication in 1. Moreover, in 3 instances where publication came first the cases presented had been collected by a national drug monitoring centre. The WHO databank has the potential to provide doctors and scientists with signals which then should be evaluated in detail.

Agranulocytosis↗

PubMed1990

Labelling toxic plants.

Explore the source record for details and available documents.

Child↗

PubMed1990

Overdose of sustained release verapamil.

Explore the source record for details and available documents.

Delayed-Action Preparations↗

PubMed1990

Survey of neurological problems with amiodarone in the New Zealand Intensive Medicines Monitoring Programme.

Early in the monitoring of amiodarone it was evident that neurological events were unexpectedly frequent. A survey was then undertaken to measure the frequency of such events and to gain some impression of their clinical importance. The method of survey was the completion of questionnaires by doctors when patients were being reviewed. There was a 63.6% response rate and questionnaires were evaluated for 408 patients. There were 192 events assessed as being adverse reactions from a group of nine types of neurological events in 112 patients. Paraesthesiae, ataxia, vertigo and tremor were the most common (7-9%). The overall rate of neurological reactions was 27.5%. The individual reactions are examined as are dose relationships.

Amiodarone↗

PubMed1990

Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine.

This study has compared the effect of repeated administration of charcoal and cholestyramine on the elimination of piroxicam. Eight young adults were given piroxicam as a single dose of 20 mg, on 3 separate occasions. On one of the occasions charcoal was also given. On another occasion cholestyramine was also administered. The mean elimination half-life after piroxicam alone was 53.1 h. This was reduced to 40.0 h by charcoal administration and to 29.6 h after administration of cholestyramine. In the second phase of the study 7 elderly subjects received piroxicam 20 mg for 14 days on two occasions. Cholestyramine administration at the end of one of the periods reduced the mean elimination half-life of piroxicam from 52.3 h to 27.3 h.

Administration, Oral↗

PubMed1990

Studies on the pharmacokinetics and mutagenic potential of rhodamine B.

Rhodamine B is used as a marker dye in herbicide sprays. There is evidence that spray operators and others may absorb rhodamine B through the skin. This study was undertaken to investigate the in vivo mutagenicity of rhodamine B, to compare the in vitro mutagenicity of two commercial preparations of the dye with that of known mutagens including rhodamine 6G and to elucidate the pharmacokinetics of rhodamine B in the rabbit. Following the i.v. treatment of adult female New Zealand White rabbits with rhodamine B (1 mg/kg body wt), the plasma concentration of rhodamine B decreased rapidly and was accompanied by the appearance of at least four fluorescent polar metabolites. These metabolites, as well as a very small amount of rhodamine B, were also present in the urine which, when tested in the Ames assay was not significantly mutagenic against Salmonella typhimurium strains TA98 and TA100 either with or without metabolic activation. Urine from a human subject who had been contaminated with marker dye was also non-mutagenic. Both commercial preparations of rhodamine B were found to be weakly mutagenic, using the same assay system. It is concluded that while appropriate hygiene measures should be exercised by users of products containing this dye, the results do not support the hypothesis that rhodamine B is a genotoxic hazard in the mammalian organism.

Adult↗

PubMed1989

ACE inhibitors and anaemia.

Explore the source record for details and available documents.

Aged↗

PubMed1989

A safety profile of controlled release naproxen tablets.

This randomised single blind controlled study examines adverse reactions to standard Naprosyn (naproxen) 750 mg daily with controlled release naproxen, Naprosyn CR, 750 mg daily, in a total of 520 patients. Overall there were no major differences between the two preparations. The reporting rate of any adverse clinical event was greater in the group taking the controlled release preparation but withdrawals from medication were similar in the two groups, for whatever reason. The main finding of the study was that patients in each decile age group, mainly between 40 and 80 years, were more likely to continue on this preparation for the full 10 weeks of the trial: 57% of patients on controlled release and 46% on plain Naprosyn completed the study. Patients over 60 years, particularly females, tended to complete the study, indicating that the simpler treatment regimen without any increase in major adverse effects is useful in the elderly who are thought to be at special risk of adverse reactions from NSAIDs. In addition, a review of spontaneous reports of adverse reactions to naproxen reported nationally to the Medicines Adverse Reactions Committee shows that the pattern has not changed over the last two years during which the controlled release formulation has been available. This experience supports the acceptability of controlled release naproxen.

Aged↗

PubMed1989

Acute toxicity of combinations of sodium dichromate, sodium arsenate and copper sulphate in the rat.

1. The intraperitoneal treatment of adult male Wistar rats with various combinations of low doses of sodium dichromate (5 mg/kg), sodium arsenate (25 mg/kg) and copper sulphate (5.9 mg/kg) tended to counteract the inherent acute toxicity of each compound. 2. The co-administration of low doses of one or more of the test compounds with a high dose of sodium dichromate (35 mg/kg), sodium arsenate (90 mg/kg) or copper sulphate (23.5 mg/kg) resulted in a significant increase in acute toxicity in comparison with that produced by the administration of high doses of dichromate, arsenate or Cu2+ alone.

Animals↗

PubMed1989

Teratogenicity of combinations of sodium dichromate, sodium arsenate and copper sulphate in the rat.

1. The teratogenicity of sodium dichromate (2 mg Cr/kg), sodium arsenate (5 mg As/kg) and copper sulphate (2 mg Cu/kg) in female Wistar rats was studied following the administration of the test compounds separately and in their various combinations on gestation day 8. 2. The test compounds administered separately and the combination of dichromate plus Cu2+ were non-fetotoxic and either non- or weakly teratogenic, whereas arsenate/Cu2+ was both weakly fetotoxic and teratogenic. 3. Dichromate/arsenate and dichromate/arsenate/Cu2+ caused a marked decrease in mean fetal weight and an increased incidence of fetal resorption and abnormality formation.

Animals↗