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Biomedical subjects

H Tukiainen

Publications and source records attributed to H Tukiainen.

At least 55 records · Page 3Linked to original sources

Pharmacokinetic comparison of a dextromethorphan-salbutamol combination tablet and a plain dextromethorphan tablet.

We compared in this double-blind crossover study the bioavailability of dextromethorphan from a dextromethorphan-salbutamol combination tablet (Redol comp) and from a plain dextromethorphan tablet (Extuson) by determining dextrorphan concentrations after single-dose oral administration in 10 healthy volunteers. The absorption of salbutamol from the combined preparation was also determined. The absorption of dextromethorphan was slightly faster from the plain dextromethorphan preparation. The peak concentration of dextrorphan was achieved at 1.5 h after Extuson and at 2 h after Redol comp (1,053.0 +/- 366.5 ng/ml and 901.5 +/- 210.9 ng/ml, NS). AUC0-12 values of dextrorphan were 4,315.6 +/- 295.0 (ng/ml)h after Extuson and 3,983.8 +/- 205.6 (ng/ml)h after Redol comp (p less than 0.05). Salbutamol was well absorbed from the combined preparation and the peak concentration was achieved at 3 h (6.57 +/- 2.95 ng/ml). Four subjects reported side-effects typical for salbutamol after the combination tablet. No side-effects were reported after the plain dextromethorphan tablet. On the basis of the present study, we conclude that the absorption of dextromethorphan from the preparations tested is almost equal and the dextromethorphan-salbutamol combination can be administered in tablet form for the treatment of cough.

Adult↗

Effect of submaximal exercise at low temperatures on pulmonary function in healthy young men.

In order to understand more fully the effect on pulmonary function of whole body exposure to cold during submaximal exercise, we measured pulmonary function indices in ten healthy male students and ten healthy male forestry workers of similar age following submaximal treadmill walking at different temperatures in a climatic chamber. After measuring the maximal aerobic capacity with a cycle ergometer test, the subjects had to walk on four separate occasions in the climatic chamber at an intensity of 70%-75% of their individual maximal heart rate; the first at normal room temperature and then randomly, either at 0 degrees C or at -20 degrees C, and vice versa. The duration of each walk was 8 min. Finally, each subject had to walk in the chamber at -20 degrees C for 17 min. Flow volume spirometry was performed at room temperature 1, 5, 10, and 20 min after exercise and the values were compared to baseline values taken prior to the last walking test. There were only minor changes in pulmonary function indices following exercise at different temperatures. Only one student showed a reduction of over 15% in peak expiratory flow rate after an 8-min walk at -20 degrees C. It seems that submaximal exercise of short duration, even at a temperature as low as -20 degrees C, does not impair pulmonary function in healthy young men.

Adult↗

The single dose and steady-state pharmacokinetics of a vadocaine tablet in healthy human volunteers.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methyl-piperidyl)-propionanilide hydrochloride; INN vadocaine) is a novel compound with antitussive and local anesthetic actions. In this study, the single dose and steady-state pharmacokinetics of vadocaine hydrochloride tablet were evaluated in 28 healthy volunteers. In part 1, the pharmacokinetics of a single dose of vadocaine hydrochloride tablet were compared with the pharmacokinetics of a vadocaine hydrochloride solution. The peak concentrations of vadocaine were achieved at 1 h both after the tablet and the solution and there were no statistically significant differences in serum concentrations or in pharmacokinetic parameters. In part 2, the steady-state pharmacokinetics of vadocaine tablet were studied using the dosage of 30 mg vadocaine hydrochloride t.i.d. for four days. The peak concentrations of vadocaine were achieved on the 1st day at 1 h (61.5 +/- 6.1 ng/ml) and on the 4th day at 1.5 h (64.5 +/- 7.9 ng/ml). According to the serum concentrations and pharmacokinetic parameters, no cumulation of vadocaine was observed. Also no side-effects were reported during the study. In conclusion, vadocaine used in the tablet form is suitable for multiple dosing and the pharmacokinetic profile is almost similar to vadocaine administered in aqueous solution.

Adult↗

Benign lymphocytic angiitis and granulomatosis.

A 37 year old woman underwent a lobectomy for a lesion with a tumour like appearance on the chest radiograph. This was shown microscopically to be benign lymphocytic angiitis and granulomatosis, a rare condition that responds well to cytotoxic drugs and has a good prognosis.

Adult↗

Comparison between oral procaterol and salbutamol in patients with bronchial asthma.

The efficacy of procaterol, a new beta 2-selective sympathomimetic drug, was compared with that of salbutamol and placebo in a double-dummy crossover study in 20 asthmatic patients. Procaterol (0.1 mg orally) was given twice daily and salbutamol (4 mg orally) 3-times a day. The study was made up of four consecutive 4-day treatment periods including two periods of plain placebo. A significant direct bronchodilating effect of both procaterol and salbutamol could be seen in PEF values, measured 4-times a day, compared with the effect of placebo (p less than 0.01 for both). Procaterol was slightly superior to salbutamol. The afternoon and evening PEF values during the procaterol period did not differ from the values during the placebo period. In symptom scores, there was significantly more tremor during the procaterol period than during the placebo period (p less than 0.01). Both procaterol and salbutamol produced more palpitation than placebo (p less than 0.05). The study shows that oral procaterol is a potent bronchodilator. The doses of procaterol and salbutamol were not equivalent. Procaterol with the dose used in the study was more potent. Despite this, the duration of the bronchodilator effect of procaterol on a twice daily dosage did not seem to be long enough in all patients.

Administration, Oral↗

Lung function in patients with tracheobronchopathia osteochondroplastica.

We have analysed the ventilatory function of seven patients with tracheobronchopathia osteochondroplastica. One patient showed reversible airflow obstruction meeting the criteria of bronchial asthma. Another two patients yielded reduced percentage forced expiratory volume (FEV%) and features of small airways obstruction. The patients' previous spirometric measurements also made the rough estimation of longitudinal changes in lung function possible during a follow-up period of 1-8 yrs (mean 4.2 yrs). Although most patients had suffered severe chest infections, no deterioration in spirometric parameters was found during the follow-up. These findings suggest that tracheobronchopathia osteochondroplastica usually has a benign course.

Adult↗

Pharmacokinetic comparison of a slow-release theophylline-hydroxyzine combination and a plain slow-release theophylline preparation.

We have compared the pharmacokinetic properties of a slow-release theophylline-hydroxyzine combination and a slow-release theophylline preparation both after a single dose administration and at steady state after the dosage of twice/day for four days in ten healthy volunteers. After a single dose, theophylline was absorbed slightly faster from the combination preparation (Retafyllin comp.) than from a plain theophylline preparation (Theo-Dur). However, in a steady state phase the pharmacokinetic profiles were quite similar. Hydroxyzine showed a slight delay in absorption from the combination preparation, but in a steady state the overall pharmacokinetic profile of hydroxyzine was similar to that of theophylline. Cumulation of either hydroxyzine or theophylline was not evident. On the basis of the present study, the slow-release combination preparation of theophylline and hydroxyzine seems suitable for twice/day dosage.

Adult↗

Granulomatous gastritis as a diagnostic problem between sarcoidosis and other granulomatous disorders.

A 59-year-old man, who suffered from achlorhydria and epigastric pains but was otherwise asymptomatic, was found to have a granulomatous lesion on the gastric mucosa suggesting sarcoidosis or a localized form of Crohn's disease. No sign of involvement of terminal ileum or rectum was detected. A liver biopsy specimen showed slight changes suggestive of granulomatous inflammation, but other signs of generalized sarcoid manifestations were absent. The patient was successfully treated with corticosteroids.

Crohn Disease↗

First human studies on the safety and antitussive activity of vadocaine hydrochloride.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is a new anilide derivative which resembles lidocaine in chemical structure. The safety and antitussive effects of this new compound were studied in 6 healthy male volunteers in the first Phase I clinical trial. Vadocaine was administered in single doses of 5, 10, 15, 20, 30 and 50 mg. At these dose levels vadocaine had no effects on the cardiovascular system, the haematological variables, blood biochemistry or urinary sediment examined as safety evaluation. The antitussive properties of the compound were studied using inhaled citric acid for induction of the cough response. The antitussive properties of vadocaine were most effective at a dose of 15 mg, although no statistical significance was found. Neither was any dose-response relationship noted. However, at this dose level vadocaine is apparently safe and its antitussive properties seem promising enough for further evaluation.

Adult↗

Pharmacokinetics of graded single doses of the novel antitussive compound vadocaine hydrochloride in healthy male volunteers.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is an anilide derivative with antitussive and local anaesthetic properties. The pharmacokinetics of this new compound were studied in two Phase I clinical trials during safety evaluation. 6 (Part I) and 8 (Part II) healthy male volunteers participated in these studies. The pharmacokinetics were studied after single oral doses of 5, 10, 15, 20, 30 and 50 mg (Part I) and 100, 200, 300, 400 and 500 mg (Part II) of vadocaine in aqueous solution. Vadocaine was rapidly absorbed at each dose level. The AUCo----infinity value and 24-h urinary recovery of intact compound increased linearly as functions of the dose. The elimination half-life varied from 2.2 +/- 0.2 h to 3.7 +/- 1.6 h in a dose range from 5 to 50 mg, and from 2.7 +/- 0.3 h to 4.0 +/- 1.0 h in a dose range from 100 to 500 mg. The peak concentration of vadocaine after the highest dose was 2317.3 +/- 31.5 ng/ml at 1 h. When higher doses were used renal clearance did not change, although total body clearance seemed to diminish. Over 90% of vadocaine is metabolized, and the metabolic pathways may become saturated at a dose of 400 mg.

Adult↗

Assessment of the safety margin of vadocaine hydrochloride in man.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is an anilide derivative with antitussive and local anaesthetic action. The safety of this new compound was studied in 8 healthy male volunteers in a Phase I clinical trial. Vadocaine was administered orally as a single dose of 50, 100, 200, 300, 400 and 500 mg. At the two highest dose levels used, 400 and 500 mg, vadocaine induced side-effects originating in the central nervous system; ECG analysis revealed small prolongations in the P-Q interval and QRS complex after 400 and 500 mg. At a dose of 500 mg the P-Q interval was prolonged by a maximum of 38% (184 ms at 0.5 h; 134 ms pre-dose). The compound had no effect on blood and urinary parameters measured for safety evaluation. On the basis of these results, a 300 mg dose of vadocaine appears to be safe in man in all respects. This dose level is 10 times the therapeutic dose (30 mg). Vadocaine is sufficiently safe for future clinical trials in patients with cough.

Adult↗

Antitussive effect of dextromethorphan and dextromethorphan-salbutamol combination in healthy volunteers with artificially induced cough.

The antitussive effects of dextromethorphan (30 mg) + salbutamol (2 mg), dextromethorphan (30 mg) alone and placebo on artificial cough induced by citric acid were compared in 19 healthy non-smoking volunteers in a double-blind crossover study. The method using inhaled citric acid with increasing concentrations to establish the cough threshold level showed an acceptable reproducibility and proved to be suitable for comparison of antitussive drugs. The cough threshold level was assessed before as well as 90 and 180 min after each medication. After placebo the cough threshold level showed no statistically significant rise. However, significant rises were shown following dextromethorphan (p less than 0.001) and the dextromethorphan-salbutamol combination (p less than 0.001). Between the treatments significant differences were shown in favour of the dextromethorphan-salbutamol combination. The results indicate that salbutamol has antitussive action enhancing the effect of plain dextromethorphan.

Adult↗

Sensitization to storage mites and other work-related and common allergens among Finnish dairy farmers.

Skin-tests with the prick technique were made on 121 dairy farmers with allergic rhinitis and/or asthma (symptomatic subjects), 64 dairy farmers without respiratory symptoms (asymptomatic subjects), and 26 non-farming controls. The antigen panel consisted of the storage mites Acarus siro, Lepidoglyphus destructor, and Tyrophagus putrescentiae, as well as other work-related allergens (cereal grains, animal epithelia, fungi and yeasts), and common allergens (house dust mite, pollens). Mean areas of weals formed by individual allergens were adjusted by analysis of covariance for age, sex, and atopic background (past or present atopic dermatitis including infantile eczema). Adjusted mean weal areas for almost all allergens, except pollens and few other allergens, were significantly larger in farmers than in non-farming controls. In contrast, only skin reactions to cow dander, to a non-dialyzed crude preparation of fodder yeast Candida utilis, and to Candida albicans distinguished symptomatic subjects from asymptomatic ones. Stepwise discriminant analysis, in which reactions to all allergens as well as age, sex, and atopy were taken into account simultaneously, revealed that reactions to a dialysed preparation of fodder yeast best distinguished symptomatic farmers from asymptomatic ones. C. utilis and C. albicans may be cross-reactive. The results imply that skin tests alone are of limited value in the search for work-related causes of rhinitis or asthma among dairy farmers. Our study confirms the importance of cow dander as an occupational allergen in dairy farming. Fodder yeast seems to be another important occupational sensitizer.

Agricultural Workers' Diseases↗

Lung function of farmers with respect to atopy and smoking.

This study was based on a sample of 1,831 farmers with no symptoms of the lower respiratory tract, which was taken from a larger survey population of 12,056 farmers. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were determined cross-sectionally in connection with health examinations at local health centres. Background data, which included age, sex, height, presence of atopic symptoms, and smoking habits, were gathered in a postal survey conducted by the Social Insurance Institution of Finland. Mean FEV1 and mean FVC were adjusted for age, sex, and height; FEV1 was also adjusted for FVC. Although atopy (defined on the basis of past or present atopic dermatitis, including infantile eczema, and/or hay fever or other allergic rhinitis) had no effect on mean FEV1, mean FVC was lower in atopic than in non-atopic subjects. Both mean FEV1 and mean FVC were lower in smokers than in non-smokers. Smoking thus influenced both FEV1 and FVC, but affected FEV1 slightly more. The effects of atopy and smoking on FVC seemed to be additive. These results, which imply that atopy may predispose obstruction of small airways, match our previous finding that atopy and smoking increase the occurrence of chronic bronchitis additively.

Adult↗

Pharmacokinetics of dextromethorphan and dextrorphan: a single dose comparison of three preparations in human volunteers.

We have carried out a single-dose comparison of three different dextromethorphan cough mixtures in 10 healthy human volunteers. Dextromethorphan was administered in a single dose of 60 mg in random order. The concentrations of dextromethorphan and its main metabolite, dextrorphan, were determined from the plasma samples using high performance liquid chromatography. The concentrations of dextrorphan were 170 times higher than the concentrations of dextromethorphan. No therapeutically significant differences were detected between the three preparations tested, and there were no great differences between the pharmacokinetic profiles of dextromethorphan and dextrorphan. The three test preparations were Resilar and Redol comp. (Remeda Pharmaceutical Co., Finland), and Extuson (Ferrosan Ab, Sweden).

Adult↗