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Biomedical subjects

P Imhof

Publications and source records attributed to P Imhof.

At least 19 recordsLinked to original sources
PubMed1990

The use of transdermal nicotine in smoking cessation.

The transdermal administration of nicotine by means of a transdermal nicotine system (TNS) affords a novel way of nicotine replacement to alleviate smoking cessation. The plasma levels of nicotine maintained with the TNS are in the range of the footpoint concentrations observed in smokers. The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support. A total of 311 smokers were treated for 3 months or 9 weeks. The abstinence rates at the end of the treatment and weaning periods were almost doubled in the TNS groups (36% and 39%) as compared to the placebo groups (23% and 20%) with a significant difference for both studies (p less than 0.05). These data suggest that the TNS can also improve the smoking cessation rates under the conditions of general medical advice, making it suitable for use outside of specialized smoking cessation centers.

Administration, Cutaneous↗
PubMed1990

Influence of acetylator status on the haemodynamic effects and pharmacokinetics of cadralazine in healthy subjects.

1. Cadralazine is a new antihypertensive agent which causes peripheral vasodilation, probably mediated by a hydrazinopyridazine metabolite. 2. The possible influence of acetylator status on the pharmacokinetics and haemodynamics of the drug was studied in six fast and six slow acetylators over a period of 24 h after administration of a single 10 mg oral dose. 3. There were no differences between the two groups in AUC and Cmax values of cadralazine and apparent metabolite, the latter defined as the sum of the free and conjugated hydrazinopyridazine. Peak plasma concentrations of these compounds were reached after 1 h. Thereafter, the concentration of the metabolite declined more slowly than that of cadralazine. 4. No effects on blood pressure were noted. Changes in heart rate and plasma renin were delayed by 3-5 h with respect to the time-course of drug and metabolite in plasma; maximum responses occurred at 4-6 h after drug administration. The extent of the increase in plasma renin activity was slightly greater in slow than in fast acetylators, but the difference was not significant statistically.

Acetylation↗
PubMed1989

Spontaneous motor activity in healthy volunteers after single doses of haloperidol.

Video recordings of the spontaneous motor activity of 6 healthy volunteers after treatment with 0.75 mg haloperidol i.v., or placebo, were transcribed into a time-series protocol of motor behaviour. Characteristic changes seen after the injection of haloperidol consisted in a reduction of the motility of the extremities and prolongation of the phases of both movement and immobility of the head. The tested dose of haloperidol induced a distinct rise in serum prolactin and sedation, but had no effects on the pharmaco-EEG or on the critical flicker-fusion frequency. Analysis of the motor phenomena evoked by neuroleptics in healthy persons and in patients may help, on the other hand, to establish correlations with the motor effects observable in preclinical investigations in animals and might also contribute towards the elucidation of the extrapyramidal side-effects of these drugs.

Adult↗
PubMed1989

[Influence of acetylation phenotype on the pharmacokinetics and pharmacodynamics data of cadralazine in normotensive subjects].

Cadralazine is a new antihypertensive drug, acting as a peripheral arteriolar vasodilator through its hydrazinopyridazine metabolite. Since this metabolite actively contributes to the activity of the drug, we administered in a double blind randomized study 10 mg/placebo o.d. to 6 healthy fast and 6 slow normotensive acetylators in order to investigate the influence of the acetylator status on hemodynamics and pharmacokinetics. Blood pressure was measured with a DINAMAP apparatus, forearm hemodynamics with a pulsed doppler and central hemodynamics with impedance-cardiography; active renin (RIA), cadralazine and its metabolite (HPLC) were measured during the 11 measurement points. The results were analysed with repeated analysis of variance (ANOVA). Heart rate significantly increased (p less than 0.001), until the 24th hour (p less than 0.05), meanwhile blood pressure and forearm hemodynamics did not change. Cardiac output was increased as a consequence of the elevation in venous return. The rise in active renin paralleled the increase in heart rate with a significant correlation (r' = 0.580, p less than 0.05). The magnitude of the increase was higher in slow than that in fast acetylators, but did no reached the significance. No differences were found for AUC, Cmax and Tmax between the two groups but the active metabolite was eliminated slower than that of cadralazine. The time course of the effects on heart rate and plasma renin was not parallel to the plasma levels of cadralazine and its metabolite. With respect to the power of the study (1-beta = 80 p. 100), no significant differences were found between the two groups.

Acetylation↗
PubMed1987

Laser Doppler flowmetry, a reliable technique for measuring pharmacologically induced changes in cutaneous blood flow?

Laser Doppler flowmetry (LDF) affords a reliable non-invasive method of investigating acute changes in total cutaneous perfusion. However, the reproducibility of measurements of resting blood flow is considered to be poor. Therefore, the potential use of LDF to monitor pharmacological influences on cutaneous perfusion over time may be limited to the investigation of drug-induced changes of the response pattern to standardized provocation procedures. The present study was undertaken to evaluate the reproducibility of cutaneous vasomotor reflexes induced by various test stimuli. Measurements were made in the morning and in the afternoon of the same day at two different skin sites (finger-tip and forearm) in six healthy subjects. Each of the following six interventions induced highly reproducible decreases of total cutaneous flow: Deep inspiration, Vasalva manoeuvre, venous occlusion, arrest of arterial blood flow (followed by reactive hyperaemia), passive head-up tilting and a cold pressor test. The decrease in blood flow was more pronounced at the finger-tip except after venous occlusion. During the cold pressor test, skin perfusion was more persistently reduced at the finger-tip than at the other site. The anatomical and functional differences in the skin between the finger-tip and the forearm may also explain the absence of reactive hyperaemia at the finger-tip. Considering the excellent reproducibility of the resting baseline values and of the changes in total blood flow after standardized provocation tests within the same day, it seems possible that LDF could be a suitable method for the short-term investigation of drug effects on circulation. The long-term day-to-day reproducibility of both baseline blood flow and vasomotor reflexes remains to be further clarified.

Adult↗
PubMed1985

Effect of nitroglycerin on blood rheology in healthy subjects.

Transdermal nitroglycerin (Nitroderm TTS 5) and a placebo were applied to 10 healthy male volunteers for 10 days. Before the first application and 6, 24, 48, 96, and 240 h thereafter, the viscosity of plasma and whole blood was measured and the packed-cell volume determined. During nitroglycerin application, the viscosity of plasma and whole blood was significantly diminished, and after 10 days it averaged 5% below the initial value. The greater the initial viscosity, the more marked was the drug-induced reduction: in 5 subjects with plasma and whole-blood viscosities near the lower limit of the normal range, there was only a temporary decrease and the values reverted to their initial levels after 4 days; in the other 5 subjects, whose whole-blood viscosities were near the upper limit of the normal range, a 10% reduction was still demonstrable after 10 days. In those subjects all values measured throughout the 10-day observation period were significantly below the initial values. The haematocrit readings followed the same pattern as the alterations in viscosity. It can be assumed, therefore, that the decrease in viscosity induced by nitroglycerin results from "internal haemodilution". The clinical relevance of the changes observed is discussed. The improvement in the rheological properties of the blood may contribute to the anti-anginal effect of Nitroderm TTS.

Adult↗
PubMed1984

The metabolic fate of [14C]oxaprotiline.HCl in man. I. Disposition and preliminary pharmacokinetics.

Absorption, biotransformation and elimination of [14C]oxaprotiline.HCl have been studied after oral administration of 50 mg doses to two human subjects. Absorption was complete, and peak blood concn. of total 14C were 590 and 297 ng equiv./ml after 3-6 h in the two subjects. After 11 days, 84 and 90% dose was excreted in urine, and a total of 98% was excreted. Peak blood concn. of unchanged oxaprotiline were 16 and 19 ng/ml before, and 167 and 207 ng/ml after enzymic hydrolysis. The blood half-life in the two subjects was 23 and 29 h. The blood concn. of the desmethyl metabolite was low (2 ng equiv./ml), but also increased after hydrolysis (11-19 ng equiv./ml). Oxaprotiline was bound (83%) in vitro to serum proteins. Sixty per cent was bound to serum albumin and 20% to alpha 1-acid glycoprotein. In urine only 1% of total 14C was present as unchanged oxaprotiline, and 0.2% as the desmethyl metabolite. After enzymic hydrolysis these increased to 48 and 6%, respectively, and after acid hydrolysis to 85 and 10%.

Administration, Oral↗
PubMed1979

Influence of vasodilators used in the therapy of heart failure on platelet aggregation.

Of the vasodilators used at present in the treatment of heart failure, only nitroprusside and phentolamine inhibit platelet aggregation at therapeutic dose levels. The other vasodilators studied, viz. nitroglycerin, isosorbide dinitrate, hydrallazine, dihydrallazine and prazosin, only inhibit platelet aggregation at relatively high concentrations, well above those reached in vivo. The exact nature of the platelet receptor, stimulation and blockade of which respectively initiate and inhibit aggregation, is not yet know, but it would appear to resemble the presynaptic alpha-receptors of other tissues.

Dihydralazine↗
PubMed1978

Effect of sulphinpyrazone (Anturan) on uric acid excretion and plasma uric acid concentration in healthy volunteers.

Investigations in six healthy volunteers given single oral doses of sulphinpyrazone (Anturan) showed that the drug had a potent uricosuric effect, even if the concentration of uric acid in the plasma was normal. In the dose range tested of 50 to 800 mg the increase in uric acid excretion was dose-related. It reached a maximum within 2 h and was still detectable 6--8 h after the drug was taken. There was a corresponding dose-related reduction in the plasma concentration of uric acid, which reached its lowest level after 8--10 h. The administration of 300 mg twice daily for four days to a further five healthy volunteers reduced plasma uric acid from 5.06 to 1.8 mg%. The findings indicate that, even if plasma uric acid levels are unknown, it would be advisable to avoid the risk of formation of urinary calculi by administering sulphinpyrazone in gradually increasing doses, ensuring adequate fluid intake and alkalinizing the urine during the first few days of treatment.

Humans↗
PubMed1978

Cardiovascular effects of tricyclic and tetracyclic antidepressants.

Cardiovascular effects of therapeutic doses of tricyclic or tetracyclic antidepressants (TCA) were examined in 66 patients. After three weeks of therapy, heart rate and PR interval were increased (P less than .02, P less than .05), while prolongation of the QTc time and the QRS interval did not reach significant levels. We observed significant flattening of T waves (P less than .05), which was not associated with changes in the serum potassium level. These changes were reversible after treatment was discontinued. When therapy was maintained for 13 months, only the heart rate continued to be increased, whereas all other ECG values had returned to normal. The TCA therapy led to a significant prolongation of the preejection period (P less than .01) and slight shortening of the left ventricular ejection time, indicating a decrease in myocardial contractility. There was no difference of effects on the values studied between tricyclic and tetracyclic antidepressants.

Adult↗
PubMed1978

Effect of propranolol on fetal tachycardia in diabetic pregnancy.

Propranolol was administered during the last 20 days of pregnancy to a diabetic woman because of fetal tachycardia (heart rate approximately 200 beats/min). With a daily dose of 160 mg of propranolol, a fetal heart rat of 120 to 160 beats/min could be achieved. Blood concentration of propranolol was measured in the mother and infant after birth. The level in the neonatal blood was 20 percent of the maternal sample, which is definitely higher than expected from animal experiments. No undersirable effect of propranolol treatment was detected. Postpartum, the infant demonstrated paroxysmal supraventricular tachycardia, and propranolol was again essential in maintaining a normal rate.

Adult↗