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Biomedical subjects

B Hallén

Publications and source records attributed to B Hallén.

At least 19 recordsLinked to original sources
PubMed1990

Pharmacokinetics of terodiline and a major metabolite in dogs with a correlation to a pharmacodynamic effect.

The pharmacokinetics and pharmacodynamics of the anticholinergic and calcium antagonistic drug terodiline, N-tert-butyl-1-methyl-3,3-diphenylpropylamine, have been studied in beagle dogs. The bioavailability was about 25% (0.15 and 0.5 mg/kg), the terminal half-life 3 hr, the systemic clearance 40 ml/min..kg, the volume of distribution (V beta) about 7 l/kg and the unbound fraction in serum 0.14. p-Hydroxyterodiline and p-hydroxy-m-methoxyterodiline were quantitated and constituted 15-40% and 25%, respectively, of the amount excreted in urine (about 60% of the dose) and were the main metabolites, as in man. The dog was used as an experimental model to study the chronotropic effect. An increased heart rate was observed after acute administration of high doses of terodiline as well as after p-hydroxyterodiline. A 20% increase in heart rate was observed at a mean serum concentration of 1086 and 1010 micrograms/l following intravenous injection of terodiline or p-hydroxyterodiline, respectively. The corresponding unbound concentrations were 150 and 474 micrograms/l. The potency ratios of terodiline/p-hydroxyterodiline was 0.9 +/- 0.2 (based on total concentrations) and 3.2 +/- 0.8 (based on unbound concentrations). The estimated potency of parent drug and main metabolite and the fact that p-hydroxyterodiline constitutes 10-20% of the terodiline steady-state level in man, indicate that the contribution of the metabolite to the chronotropic effect observed in clinical studies is minor.

Administration, Oral↗
PubMed1989

Tolerability and steady-state pharmacokinetics of terodiline and its main metabolites in elderly patients with urinary incontinence.

The elderly form an important target group for the treatment of urinary urge incontinence with drugs such as terodiline (Mictrol, Terolin). In order to evaluate its steady-state pharmacokinetics and tolerability in geriatric patients terodiline 12.5 mg b.d. was given to 28 hospitalized patients with urinary incontinence (mean age 85 years) for six weeks. The patients were monitored during the study and for 6 weeks afterwards, blood samples being taken at regular intervals. In addition to these multi-diseased and polymedicated patients, a small, homogenous group of healthy volunteers (mean age 40 years) was studied as a reference group, being given terodiline 12.5 mg b.d. for 2 weeks. Terodiline was generally well tolerated by the patients and no significant change in blood pressure or heart rate were found. One patient was withdrawn due to adverse effects. The mean terminal half-life of terodiline was 131 h and the clearance after oral administration (clearance/systemic availability) was 39 ml.min-1. The corresponding figures for the healthy volunteers were 57 h and 75 ml.min-1. The average steady-state serum concentration was 518 micrograms.l-1 in the geriatric patients and 238 micrograms.l-1 in the healthy volunteers. Steady-state was reached within 3 weeks in 20 of the 28 patients and within 5 weeks in 7 patients. In the geriatric patients the steady-state serum concentration of the main metabolite p-hydroxyterodiline, during the last three weeks on terodiline was 45 micrograms.l-1, 57 micrograms.l-1, and 45 micrograms.l-1, respectively, and a similar value was found in the healthy volunteers, 47 micrograms.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Single- and multiple-dose pharmacokinetics of terodiline in geriatric patients.

As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previously found (Hallén et al. 1987) in healthy volunteers (mean age 35 years). There were higher peak serum concentrations (110 vs 79 micrograms.l-1), increased half-life (189 vs 60 h), lower renal clearance (4.0 vs 10.9 ml.min-1) and lower total clearance (29 vs 75 ml.min-1). Multiple-doses of 12.5 mg b.d. for 6-8 weeks resulted in a mean steady-state concentration of 642 micrograms.l-1, which was in agreement with the single dose parameters. The studied geriatric patients can be characterized not only as old, but also as frail, bedridden, having several diseases and polymedicated. The differences in pharmacokinetics between younger and elderly subjects can be attributed to a variety of complex factors, which may alter the clearance and/or the volume of distribution.

Aged↗
PubMed1988

Cardiac arrest during anaesthesia. A computer-aided study in 250,543 anaesthetics.

With the aid of a computer-based anaesthetic record-keeping system, all cardiac arrests during anaesthesia at the Karolinska Hospital between July 1967 and December 1984 were retrieved. There were a total of 170 cardiac arrests and 250,543 anaesthetics in the data file, which gives an incidence of 6.8 cardiac arrests per 10,000 anaesthetics. Sixty patients died, constituting a mortality of 2.4 per 10,000 anaesthetics: 42 were considered as inevitable deaths (rupture of aortic or cerebral aneurysm, multitrauma, etc.); 13 cases of cardiac arrest were considered as non-anaesthetic, i.e. complications due to surgery and other procedures. Nine of these patients died. 115 cases of cardiac arrest were considered as caused by the anaesthetic and nine of these patients died. Thus mortality caused by anaesthesia was 0.3 per 10,000 anaesthetics. The most common cause of cardiac arrest due to anaesthesia was hypoxia because of ventilatory problems (27 patients), postsuccinylcholine asystole (23 patients) and post-induction hypotension (14 patients). The highest mortality was seen when spinal or epidural anaesthetics were given to patients with impaired physical status including hypovolaemia. The incidence of cardiac arrest has declined considerably during the period studied, and this coincides with an increasing number of qualified anaesthetists employed in the department during the same period.

Aged↗
PubMed1988

Relationship between gastric emptying and serum concentrations of emepronium in dogs and human volunteers.

Clinical trials with increased dosages, relative to the standard regimen, of the anticholinergic drug emepronium (Cetiprin Novum) resulted in a clear improvement in micturition- and urodynamic parameters in urinary incontinent patients. In the present study possible effects on the gastric emptying were tested in dogs and in human volunteers. In dogs a wide dose range of emepronium (5-100 mg/kg p.o.) was used to establish a relationship between serum concentration and effect on the gastric emptying. Gastric emptying was slightly decreased after 25 mg/kg (peak conc. of emepronium about 100 micrograms/l) and markedly decreased after 50 mg/kg (500 micrograms/l) and 100 mg/kg (5000 micrograms/l). In the volunteers no effect of emepronium on gastric emptying was observed, either after 200 mg q.i.d. or after 400 mg q.i.d. (about 3 and 6 mg/kg q.i.d.), which resulted in peak serum concentrations of 100-300 micrograms/l).

Adult↗
PubMed1987

Propofol vs thiopentone as anaesthetic agents for short operative procedures.

In a randomized open study, 120 healthy female patients were included. For short gynaecological procedures they were anaesthetized with either propofol 2.5 mg X kg-1 (n = 60) or thiopentone 5 mg X kg-1 (n = 60) in combination with nitrous oxide/oxygen (67%/33%). Supplementary doses of propofol (10-20 mg) or thiopentone (25-50 mg) were given when necessary during the procedure. Induction characteristics for propofol and thiopentone 1 min after start of induction were similar. Propofol seemed to have a more depressant effect than thiopentone on the circulatory response to anaesthesia. Recovery times from the end of the operative procedure until the patients opened their eyes on command and were orientated were shorter in the propofol patients compared to the thiopentone patients. In the propofol group, patients recalled discomfort on injection more often than patients anaesthetized with thiopentone. Otherwise, the side-effects were similar in both groups. We conclude that propofol is similar to thiopentone in its anaesthetic qualities during induction and maintenance of short anaesthetic procedures. Propofol was associated with a more rapid emergence from anaesthesia than thiopentone.

Anesthesia, Intravenous↗
PubMed1987

Gastrointestinal transit rate-related absorption of emepronium: a study in mice.

The gastrointestinal (GI) absorption in mice of the anticholinergic quaternary ammonium compound emepronium, assessed by the urinary excretion of radioactivity and unchanged drug, increased from 1% to 7% and from 0.5% to 5%, respectively, in the dose range 0.1 to 40 mg/kg, whereafter a plateau was reached. Changes in the metabolism were evident at doses exceeding 80 mg/kg when 80% of the radioactivity was excreted as unchanged emepronium, as compared to 50% at lower doses. No dose-dependent urinary excretion of radioactivity was detected following intravenous injection. The increase in the fraction of the dose excreted in the urine after oral administration therefore cannot be easily explained by a dose-dependent metabolism or renal excretion. However, a relationship was seen between the reduced gastrointestinal motility, produced by increasing doses of the drug, and the increased bioavailability. Atropine sulphate given subcutaneously (1-50 mg/kg) more than doubled the urinary recovery of a small pharmacologically inactive oral dose of emepronium (5 mg/kg) and thus confirmed the transit rate-dependent absorption of emepronium. The superimposed effect of the pharmacological action on the GI transit rate, derived from the inherent property of an anticholinergic drug, may be of special significance for a drug with a low degree of absorption and a high variability, such as has been observed in clinical trials with the quaternary drug emepronium (Cetiprin).

Animals↗
PubMed1987

Species differences in the intestinal excretion of emepronium.

A substantial proportion of a parenteral dose of emepronium given to dogs is excreted via the gastrointestinal tract by biliary excretion and by excretion through the intestinal mucosa (Hallén et al. 1979). In the present paper the different routes of elimination were further investigated in mouse and man and compared to the dog. The disposition of emepronium-derived radioactivity (14C) in the three species showed that about 45% was excreted via urine and 55% via faeces. The proportion of the faecal excretion of 14C that could be referred to the intestinal route differed between the species and was about 20% in man, 60% in the mouse and most pronounced, 80%, in the dog.

Aged↗
PubMed1985

Clinical study of a lignocaine-prilocaine cream to relieve the pain of venepuncture.

The efficacy of a topical anaesthetic formulation, EMLA 5% cream (Eutectic Mixture of Local Anaesthetics) in obtunding the pain produced by venepuncture, was determined in a double-blind randomized, cross-over study in 31 adult volunteers. Pain was registered on a 10-cm visual analogue scale. In each subject the mean pain score after treatment with EMLA was compared with that following placebo. Twenty-eight subjects had lower pain scores with EMLA, and in the remaining three subjects EMLA and placebo were equi-effective. Transient skin reactions (blanching, erythema and oedema) were observed with both formulations. These reactions were not found to be aggravated by repeated applications.

Administration, Topical↗
PubMed1985

Plasma fluoride and bromide concentrations during occupational exposure to enflurane or halothane.

The plasma fluoride and bromide concentrations were studied in operating theatre personnel. When enflurane was used, the increase in plasma fluoride concentration could not be distinguished from normal individual variations, but the plasma bromide concentration increased significantly when halothane was used. Seven patients were exposed to enflurane in a concentration of 200 parts per million for 4 h. A significant increase in the plasma concentration of fluoride was observed. The peak concentrations of fluoride occurred during exposure and the increase lasted less than 12 h. The increase in fluoride concentration was larger at this trace concentration than reported after anaesthetic concentrations. Cerebrospinal fluid (CSF) fluoride concentration was also studied; a smaller and delayed increase was found in CSF compared to plasma.

Air Pollutants, Occupational↗
PubMed1985

Ion pair formation and gastrointestinal absorption of emepronium.

Ion pair forming agents were evaluated in vitro for their ability to form lipophilic ion pairs with the quaternary ammonium compound emepronium and in vivo to enhance its gastrointestinal absorption. A 5- to 100-fold excess of trichloroacetate (TCA), diethylhexylphosphate (DEHPA), heptafluorobutyrate (HFBA), sodium lauryl sulphate (SLS), bromide or chloride all increased the extractability of the emepronium ion into methylene chloride. The additive with the most marked effect on the apparent partition coefficient of emepronium (Kapp) was SLS. At emepronium 10(-4) M, Kapp increased from a basal value of 0.1 to 368 with a 100-fold molar excess. However, the increased partitioning to methylene chloride was not reflected in an increased gastrointestinal absorption of the emepronium ion when this was given orally to mice. When intestinal juice, instead of distilled water or buffer, was used as the aqueous phase, the partition coefficient was markedly higher (Kapp approximately 2) but it was significantly less influenced by addition of sodium lauryl sulphate (Kapp approximately 6). The preexisting positive influence of the intestinal juice on the lipophilic character of emepronium and the rather limited additive effect of agents that form lipophilic complexes with emepronium, lead to the conclusion that the ion pair concept is not a suitable approach to enhance the gastrointestinal absorption of this drug.

Animals↗
PubMed1984

Pain-free venepuncture. Effect of timing of application of local anaesthetic cream.

This study was designed to assess the effect of time on the analgesic effect of a local anaesthetic cream consisting of a mixture of 5% lignocaine and prilocaine. The cream and placebo were compared in a double-blind, randomized study in 114 children aged 4-17 years, with application times of 20 minutes and longer. A regression analysis revealed no difference in analgesic effect between cream and placebo when application times were less than 60 minutes. A cusum test showed that the effect of the cream became evident at about 60 minutes. Local adverse reactions consisted mainly of transient paleness of the skin, which did not constitute any clinical problem.

Adolescent↗
PubMed1983

The effect of local scavenging on occupational exposure to nitrous oxide.

Despite evacuation of excess anaesthetic gases at the expiratory valve of the anaesthetic circuit and a general ventilation system producing 17-20 air changes per hour, mask anaesthesia often causes occupational exposure to anaesthetic gases exceeding the threshold limit values. The effect of a local air exhaust system, a local scavenger, on occupational exposure to nitrous oxide during paediatric mask anaesthesia was studied. The scavenger evacuated 140 m3 of air per hour and was placed at a distance of 20 cm from the face mask. In a very poorly ventilated operating theatre the exposure to nitrous oxide was reduced by 75% during the anaesthetic sessions and exposure to concentrations above 500 ppm was almost eliminated. The experiences from the installation and clinical use are discussed. Local scavenging is an excellent complement to the scavenging of excess gases at the expiratory valve, and it may be considered an alternative to expensive, high-capacity ventilation systems.

Air Conditioning↗
PubMed1983

Thermocamera studies of nitrous oxide dispersion in the dental surgery.

Nitrous oxide is used in dentistry for sedation and analgesia. Chronic occupational exposure of dental personnel to trace concentrations of nitrous oxide has been reported as a potential health hazard. A new application of the thermocamera technique was used to study the dispersion of nitrous oxide during dental analgesia. Four breathing systems with different evacuation systems were tested and found to vary in scavenging efficiency. A local exhaust system ensured minimal exposure when nitrous oxide leaks contaminating the air in the dentist's breathing zone occur.

Air Pollutants↗