The role of antifungals in the management of patients with severe asthma.

In patients with asthma, the inhalation of elevated amounts of fungal spores and hyphae may precipitate the onset of asthma or worsen control to the extent of being life-threatening. Sensitisation to fungi, especially Aspergillus fumigatus, is found in 15% to 48% of asthmatics in secondary care and is linked to worse asthma control, hospitalisation, bronchiectasis and fixed airflow obstruction, irrespective of whether allergic bronchopulmonary aspergillosis (ABPA) is diagnosed. ABPA represents a florid response to the presence of Aspergillus spp.

The influence of diet upon liver function tests and serum lipids in healthy male volunteers resident in a Phase I unit.

Aim: To investigate the effect of diet upon liver function tests and serum lipids within the restricted environment of a Phase I unit.

Methods: An open randomized three-way crossover study was designed with subjects consuming three types of diet. The diets comprised, a balanced normal calorie diet, a high-carbohydrate high-calorie diet and a high-fat high-calorie diet.

Enzyme-induction dependent bioactivation of troglitazone and troglitazone quinone in vivo.

Troglitazone (TGZ), a 2,4-thiazolidinedione antidiabetic, causes hepatotoxicity in 1.9% of patients. TGZ is an inducer of, and substrate for, hepatic P450 3A.

Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol.

Unlabelled: This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects.

Method: All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg/day from Days 9 to 16, and remained at 200 mg/day for the final 10 days of the drug administration period.

Absence of effect of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin.

Unlabelled: A double-blind, randomized, placebo-controlled study assessed the effects of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin in 30 healthy male volunteers.

Method: All subjects received phenytoin throughout the study. The dose of phenytoin was 100 mg three times daily; steady-state trough plasma phenytoin concentrations were determined on Day 6.

Absence of a sertraline-mediated effect on the pharmacokinetics and pharmacodynamics of carbamazepine.

Unlabelled: A double-blind, randomized, placebo-controlled study was conducted in 14 healthy male volunteers to assess the effects of sertraline on the pharmacokinetics and pharmacodynamics of carbamazepine.

Method: Subjects received carbamazepine 200 mg once daily for 2 days and every 12 hours thereafter. On Days 16 to 32, subjects also received either sertraline or placebo daily.

Absence of a sertraline-mediated effect on digoxin pharmacokinetics and electrocardiographic findings.

Unlabelled: The effects of oral administration of sertraline on the plasma concentration profile and renal clearance of digoxin were assessed in 20 healthy male subjects in a double-blind, randomized study.

Method: All subjects first received digoxin 0.5 mg twice daily on Day 1, 0.

The effect of tenidap on the anti-hypertensive efficacy of ACE inhibitors in patients treated for mild to moderate hypertension.

1. A randomised, placebo controlled, double-blind, parallel group study was conducted to assess the effect of tenidap sodium, a novel cytokine modulating drug, on the stable hypotensive response to the angiotension converting enzyme (ACE) inhibitor enalapril in subjects with mild to moderate, uncomplicated, essential hypertension. 2.

The effect of tenidap on the anti-hypertensive efficacy of thiazide diuretics in patients treated for mild to moderate hypertension.

1. This randomised, placebo-controlled, double-blind, parallel-group study was conducted to assess the effect of tenidap sodium 120 mg, a novel anti-arthritic cytokine modulating drug, on the hypotensive efficacy of the thiazide diuretics hydrochlorothiazide or bendrofluazide. 2.

Effect of tenidap sodium on digoxin pharmacokinetics in healthy young men.

1. The effects of tenidap sodium and placebo on digoxin pharmacokinetics were compared in 14 healthy young men, in a double-blind, parallel-group study lasting for 24 days. 2.

A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response.

As part of an open dose-ranging study, the pharmacokinetics of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist given by the i.v. route, was studied in 18 patients receiving highly emetogenic cytotoxic drugs, predominantly cisplatin, either alone or in combination with other cytostatic agents.

Pharmacokinetics and anti-emetic efficacy of BRL43694, a new selective 5HT-3 antagonist.

Twenty patients receiving a variety of emetogenic cytotoxics (including cisplatin in 5) were given a single i.v. infusion of 40 micrograms kg-1 of BRL43694 (as the hydrochloride salt) in successive groups of 3-4 patients between 0-6 hours after chemotherapy.

The effects of serum, lithium, ethacrynic acid, and a low external concentration of potassium on specific [3H]-ouabain binding to human lymphocytes after incubation for 3 days.

We have quantified specific [3H]-ouabain binding sites in normal human lymphocytes, and have measured the changes in the numbers of those sites which occur in response to various stimuli. We have confirmed previous findings that incubation for 72 h in the presence of fetal calf serum causes an increase in [3H]-ouabain binding, and that this does not occur if the cells are incubated in fetal calf serum which has first been dialysed. During incubation of the lymphocytes for 3 days in the presence of dialysed fetal calf serum each of the following stimuli caused an increase in specific [3H]-ouabain binding: addition of ethacrynic acid (1 mumol l-1), addition of lithium (1 mmol l-1), and reduction of the external potassium concentration (to 0.

Clinical pharmacokinetics of allopurinol.

Allopurinol is a widely used drug in the management of hyperuricaemia. It is rapidly and extensively absorbed following oral administration. The major and active metabolite, oxypurinol, is detected in the circulation within 15 minutes of allopurinol administration.

Clinical pharmacokinetics of bretylium.

Bretylium is a class III antiarrhythmic agent which is used for the management of serious and refractory ventricular tachyarrhythmias. It exhibits a complex pharmacokinetic profile which is poorly understood. The drug is poorly absorbed following oral administration, and its oral bioavailability is in the region of 18 to 23%.

Treatment of intractable neurogenic pain with carbamazepine.

Sixteen patients with previously intractable neurogenic pain were treated with carbamazepine (CBZ) for a period of six weeks. CBZ initial daily dosage of 400 mg was increased by a similar amount every second week to a maximum of 1,200 mg. Single dose kinetic studies prior to initiating CBZ therapy showed that these patients metabolised the drug similarly to healthy controls.

Effect of carbamazepine on haem biosynthesis in man.

The effects of the enzyme-inducing anticonvulsant carbamazepine on haem biosynthesis in healthy male subjects is reported. A dose-dependent increase in the activity of leucocyte delta-aminolaevulinic-acid synthase, the rate-limiting enzyme of haem biosynthesis, was noted following 400 and 600 mg carbamazepine daily in the same eight subjects. This rise was maximal after 1 week's treatment (400 mg: 509% +/- 285 of baseline; 600 mg: 1062% +/- 170 of baseline; P less than 0.

Changes in circulating androgens during short term carbamazepine therapy.

Serum concentrations of testosterone, androstenedione, dehydroepiandrosterone sulphate (DHAS), sex hormone binding globulin (SHBG) and luteinising hormone (LH) were measured before, during and after 21 days treatment with carbamazepine (CBZ)400 mg daily in six healthy male subjects. Induction of hepatic microsomal enzyme activity was confirmed by an increase in antipyrine clearance (P less than 0.02) and a fall in circulating CBZ concentrations from the seventh to the fourteenth CBZ dose (P less than 0.

Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine.

The effect of short-term hepatic enzyme induction with carbamazepine (CBZ) on circulating thyroid hormone concentrations was studied in 10 healthy male subjects. CBZ 400 mg per day was given for 21 days in 6 subjects and for 14 days in a further 4. In the former group the effect of therapy on the pituitary/thyroid axis was also assessed by measuring thyroid stimulating hormone (TSH) response to thyrotrophin-releasing hormone.

Carbamazepine 10, 11 epoxide concentrations in epileptics on carbamazepine alone and in combination with other anticonvulsants.

Steady state carbamazepine (CBZ) plasma concentrations were similar in 15 epileptics receiving monotherapy and in 24 patients taking CBZ in combination with one other anticonvulsant. The ratio of CBZ 10, 11-epoxide (CBZ-E) to the parent drug was significantly higher (P less than 0.01) in those patients taking concomitant phenytoin (n = 9), phenobarbitone or primidone (n = 9), and valproic acid (n = 6) than in the patients receiving CBZ alone.