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Biomedical subjects

D N Bateman

Publications and source records attributed to D N Bateman.

At least 109 records · Page 6Linked to original sources
PubMed1988

Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis.

1. The rate of onset and magnitude of the effect of levocabastine, a potent H1-receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis.

Adult↗
PubMed1988

Allopurinol kinetics after massive overdosage.

A 15-year-old girl with normal renal function took 75 tablets of allopurinol 300 mg. She did not suffer any ill-effects. Samples obtained over 84 h showed prolonged elimination of allopurinol, with a half-life of 3.6 h, and oxipurinol, with a half-life of 26 h.

Adolescent↗
PubMed1988

Population analysis of the pharmacokinetic variability of high-dose metoclopramide in cancer patients.

Metoclopramide infusions are used to prevent nausea and vomiting in cancer patients during chemotherapy. 47 patients received metoclopramide during 109 chemotherapeutic treatments as a loading (dose range = 0.55 to 4.5 mg/kg over 15 minutes) and maintenance (dose range = 0.57 to 4.8 mg/kg over 8 hours) infusion. During and up to 24 hours after the end of the maintenance infusion between 4 and 10 blood samples were collected per treatment. Metoclopramide was analysed in plasma by liquid chromatography. Pharmacokinetic and demographic data of 83 treatments were analysed by the NONMEM program using a linear 2-compartment model. It was found that bodyweight and serum alkaline phosphatase activity explain some of the interindividual variability in clearance (CL). The typical pharmacokinetic parameters for an average individual (70kg, alkaline phosphatase = 100 IU/L) were: CL = 20 L/h; volume of distribution at steady state (Vdss) = 190L; terminal half-life = 8h. The interindividual variabilities in clearance, volume of central compartment and Vdss were 50%, 35% and 35%, respectively. The residual variability in plasma concentrations was estimated as 13%.

Antineoplastic Agents↗
PubMed1987

Interaction of cimetidine with oral melphalan. A pharmacokinetic study.

The effects of pretreatment with cimetidine (200 mg three times daily, 400 mg at night) on the pharmacokinetics of oral melphalan (10 mg) have been investigated in patients with multiple myeloma. Cimetidine pretreatment reduced the bioavailability of oral melphalan by approximately 30% (P less than 0.05). The elimination rate of melphalan from plasma was significantly increased by cimetidine (P less than 0.05), the half-life being reduced from 1.94 +/- 0.55 h to 1.57 +/- 0.53 h. Cimetidine appeared to reduce the interindividual variability in melphalan absorption, but at the cost of reduced bioavailability.

Administration, Oral↗
PubMed1987

High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy.

We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy. Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations. In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor. There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophosphamide and doxorubicin. The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration. Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.

Adult↗
PubMed1987

Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers.

The pharmacokinetics and pharmacodynamics of prochlorperazine were studied in healthy volunteers using a recently developed h.p.l.c. assay. Eight subjects received 12.5 mg and 6.25 mg i.v. doses of prochlorperazine, a 25 mg oral dose and placebo in random order. Plasma half-life (t1/2) of prochlorperazine was 6.8 +/- 0.7 h and 6.9 +/- 0.8 h for the 12.5 mg and 6.25 mg i.v. doses respectively. Apparent volume of distribution and plasma clearance were high and the kinetics did not appear to be dose-related. Absorption of oral prochlorperazine appeared to be slow and bioavailability was very low. A metabolite, possibly prochlorperazine sulphoxide, was noted after oral dosing. Mild sedation was common after i.v. prochlorperazine, but cardiovascular effects were minimal. The main adverse effect was akathisia which was reported by five out of eight subjects after the higher i.v. dose. These results provide preliminary information on the pharmacokinetics of i.v. prochlorperazine which were previously unknown.

Administration, Oral↗
PubMed1987

Effects of time of dosing and age on intravenous aminophylline pharmacokinetics.

The elimination kinetics of theophylline were investigated following intravenous administration of aminophylline in 12 subjects (six fit young, and six healthy hospitalised elderly volunteers) at 09.00 h and 21.00 h on separate occasions at least 5 days apart to determine whether time of administration had significant effects on clearance in young and elderly subjects. We were unable to demonstrate a significant change in kinetic parameters between morning and evening administration in either young or elderly subjects. Our results also demonstrated no difference in kinetics between young and elderly subjects. We conclude that neither time of dosing nor age are important determinants of theophylline elimination kinetics in healthy subjects.

Adult↗
PubMed1987

Pharmacological treatments of paraquat poisoning.

A large number of pharmacological techniques aimed at modifying paraquat toxicity have been investigated. There is no convincing controlled evidence that any are unequivocally useful. Studies with an ascorbic acid and riboflavin combination appear effective in rats, and there is a suggestion that cyclophosphamide and dexamethasone may in some way alter paraquat toxicity in man and by pretreatment, but not concurrent treatment, also in the rat. Further controlled studies are required of these treatments in patients who are potentially salvageable. There is a need for a rapid paraquat assay for clinical use in order that patients in this category can be identified quickly and included in appropriate controlled studies.

Animals↗
PubMed1987

Age and self-poisoning: the epidemiology in Newcastle upon Tyne in the 1980s.

The epidemiology of 737 consecutive self-poisoning admissions to Freeman Hospital, Newcastle upon Tyne, has been investigated with reference to age in young (less than 35), mid-aged (35-64) and elderly (greater than or equal to 65 year) patients. The most important differences were increased formal psychiatric illness in the elderly, demonstrated by increased likelihood of admission to psychiatric units; less likelihood of overdose with multiple agents in the elderly, and less use of alcohol. There were also differences in the types of drugs used. The youngest patients took more paracetamol and less psychoactive drugs and more of their drugs were prescribed for a relative than the other two groups. The elderly were much less likely to receive gastric lavage or emesis and more likely to receive supportive treatment only than younger patients. This difference may, in part, be explained by the more frequent occurrence of benzodiazepine poisoning in those over 65 years.

Adolescent↗
PubMed1986

The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam.

The effects of the benzamide cisapride (C) (8 mg) i.v. have been compared to placebo (P) in a double blind randomised study. The effects on gastric emptying, the absorption and effects of oral diazepam, and BP and pulse were observed. Cisapride increased the rate of gastric emptying of 500 ml liquid containing diazepam 10 mg (t 1/2 C: 7.4 min, P: 14.9 min). The initial rate of absorption of diazepam contained in the drink was increased by C (AUC 0-1 h C: 328 micrograms h l-1, P: 253 micrograms h l-1, but there was no change in overall bioavailability. This change in diazepam kinetics was associated with a significantly greater impairment in reaction time in the first 45 min after drinking but not in self rated sedation. Cisapride produced a significant tachycardia (e.g. after 10 min C: 82 beats/min, P: 69 beats/min) which probably reflects a peripheral vasodilator action. Cisapride may therefore alter the pharmacokinetics and dynamics of concurrently administered drugs.

Adult↗
PubMed1986

Oral bioavailability of high-dose metoclopramide.

The oral bioavailability of high-dose metoclopramide was studied in 12 patients, who received oral or intravenous (i.v.) metoclopramide in random order with each of 2 consecutive courses of cytotoxic chemotherapy. The terminal half-life of metoclopramide was 7.1 +/- 0.4 h (mean +/- SEM) and was not affected by the route of drug administration. Mean bioavailability was 86.6 +/- 4.7% and the range (65-118%) was less than that reported for standard doses. Neither half-life nor bioavailability was significantly correlated with age. Adverse effects were mild and were similar for both oral and iv metoclopramide. Oral high-dose metoclopramide, given in the same doses as for i.v. administration, should therefore be as effective as the i.v. regimen and may be easier to administer.

Adult↗
PubMed1986

The plasma protein binding of metoclopramide in health and renal disease.

The plasma protein binding of metoclopramide was measured after addition of the drug (60 ng ml-1) to plasma from 18 patients with renal disease and 18 age and sex matched healthy individuals. The mean free fraction in renal disease (0.59 range 0.41-0.71) was not significantly different from controls (mean 0.6 range 0.56-0.69). In both groups the binding ratio of metoclopramide was significantly related to plasma alpha 1-acid glycoprotein (AAG) concentration but not to albumin or plasma non-esterified fatty acids concentration. Metoclopramide bound to human serum albumin (HSA) to a limited extent and to human AAG to a greater extent indicating that AAG is the major binding protein for the drug in plasma.

Blood Proteins↗
PubMed1986

Charcoal-column haemoperfusion does not significantly enhance chlormethiazole removal.

A 26-year-old man had convulsions after taking an overdose of slow-release aminophylline tablets. The convulsions were treated with an infusion of chlormethiazole and theophylline was removed by charcoal-column haemoperfusion. It has been suggested that haemoperfusion might be useful for removing chlormethiazole and this was investigated. There was no evidence that charcoal-column haemoperfusion could remove clinically significant amounts of chlormethiazole.

Adult↗
PubMed1986

Quinine toxicity.

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Abortifacient Agents↗
PubMed1986

Extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom.

The epidemiology of extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom has been studied using reports in the Adverse Reactions Register of the Committee on the Safety of Medicines (CSM) and from general practitioner prescribing data. Between 1967 and 1982 there were an estimated 37.0 million prescriptions for prochlorperazine and 3.2 million for haloperidol; in this time there were 104 reports of adverse reactions to prochlorperazine and 62 to haloperidol. The predominant extrapyramidal reaction reported was dystonia-dyskinesia (99 reports for prochlorperazine and 47 for haloperidol). The remaining reactions reported were of Parkinsonism. Dystonia-dyskinesia usually occurred within three days of commencing treatment, and for both drugs the incidence, expressed per million prescriptions, varied significantly with age, the highest incidence being in patients under 20 years. Thus young patients appear at particular risk of acute extrapyramidal reactions to dopamine receptor antagonists.

Adolescent↗
PubMed1985

Extrapyramidal reactions with metoclopramide.

The epidemiology of extrapyramidal reactions to metoclopramide was studied by examining reports in the Adverse Reactions Register of the Committee on the Safety of Medicines and comparing these with prescribing figures by general practitioners in the United Kingdom for metoclopramide (Maxolon). In the period 1967-82 there were an estimated 15.9 million prescriptions and 479 reports of extrapyramidal reactions (455 of dystonia-dyskinesia, 20 of parkinsonism, and four of tardive dyskinesia). When corrected for prescribing rates the relative risk of dystonia and dyskinesia was 1.8 in female compared with male patients (95% confidence interval 1.4-2.2). The overall reporting rate for dystonia and dyskinesia was 28.6/million prescriptions but was significantly more common in young adults (p less than 0.0001) and especially girls and women aged 12-19 (190.7 reports/million prescriptions). By contrast parkinsonian reactions were significantly more common in the elderly (p less than 0.0001).

Adolescent↗