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Clinical Pharmacology and Therapeutics Jul 1984The specific airway conductance (sGaw) response of eight normal men to inhaled salbutamol, 200, 600, and 1800 micrograms, was measured on 3 separate days. On each... (Comparative Study)
Comparative Study
The specific airway conductance (sGaw) response of eight normal men to inhaled salbutamol, 200, 600, and 1800 micrograms, was measured on 3 separate days. On each occasion subjects received either placebo, long-acting propranolol (160 mg), or penbutolol (40 mg) orally in a double-blind manner after baseline lung function determination. After placebo, mean sGaw rose from a baseline of 2.07 +/- 0.15 to 2.81 +/- 0.25 kPa-1 X sec-1 after 200 micrograms salbutamol. There was little further airway dilation with higher doses of salbutamol. With long-acting propranolol, there was no significant airway dilation after 200 micrograms salbutamol but there was after 600 and 1800 micrograms inhaled salbutamol; baseline sGaw rose from 2.02 +/- 0.17 to 2.70 +/- 0.28 and 2.95 +/- 0.32 kPa-1 X sec-1. Penbutolol prevented any significant airway dilation with all doses of salbutamol. Penbutolol at the doses used appears to be a more potent blocker of beta 2-receptors than does propranolol.
Topics: Adult; Albuterol; Blood Pressure; Bronchi; Dilatation; Double-Blind Method; Drug Interactions; Heart Rate; Humans; Male; Penbutolol; Propanolamines; Propranolol
PubMed: 6734048
DOI: 10.1038/clpt.1984.137 -
European Journal of Drug Metabolism and... 1988Penbutolol is a not cardioselective beta-adrenergic blocking drug; it is lipid soluble and differs in its protein binding from the other members of its group because...
Penbutolol is a not cardioselective beta-adrenergic blocking drug; it is lipid soluble and differs in its protein binding from the other members of its group because shows linkage to alpha 1-glycoprotein, with no detectable binding to albumin. AAG levels change during pregnancy and so the binding of [3H]-penbutolol was compared in 11 pregnant patients and in 10 healthy women. Binding was obtained by ultrafiltration and measurement of the free fraction by scintillation spectrometry. The free penbutolol fraction was significantly higher in the pregnant women than in the controls (6.06 +/- 0.34 compared with 3.55 +/- 0.29, P less than 0.001). The AAG levels in the pregnant women were significantly lower (0.40 +/- 0.03 g/l) than in the controls (0.77 +/- 0.06 g/l) (P less than 0.001) which showed a significant correlation with the bound/free penbutolol ratio (r = 0.61, P less than 0.005). On the other hand there was no significant correlation with the extent of penbutolol's protein binding even though the albumin levels were lower in the pregnant women (2.83 +/- 0.17 compared with 4.86 +/- 0.17; P less than 0.001). Penbutolol's nK1a for AAG was lower in pregnant women, and this suggests that the fall in AAG levels is not the only factor involved in the reduced binding of penbutolol in pregnancy.
Topics: Adult; Blood Proteins; Contraceptives, Oral, Hormonal; Drug Interactions; Female; Humans; Orosomucoid; Penbutolol; Pregnancy; Propanolamines; Serum Albumin
PubMed: 3396610
DOI: 10.1007/BF03189924 -
Acta Cardiologica 1988We investigated the effect of an orally administered, long-acting, beta-adrenergic blocking agent, penbutolol, on the circadian rhythm of blood pressure (BP) and heart...
We investigated the effect of an orally administered, long-acting, beta-adrenergic blocking agent, penbutolol, on the circadian rhythm of blood pressure (BP) and heart rate (HR), and plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) levels in hospital patients with essential hypertension validated by a chronobiological inferential statistic method. After a wash-out period of three weeks, a group of 8 hypertensive patients (5 women and 3 men, 27 to 41 years old) underwent automatic BP and HR monitoring, and blood sampling for 24 hours in a hospital room before and after 4 weeks of treatment with penbutolol (40-mg tablet once a day at 9 a.m.). In basal conditions, a statistically significant mean circadian rhythm was demonstrated for HR, diastolic BP, PRA, PA, and PC. Systolic and diastolic BP were lowered by penbutolol, with only a minor decrease of HR. The treatment eliminated also the mean circadian rhythm of BP and HR. Penbutolol induced both a remarkable reduction of PRA with disappearance of the related circadian rhythm and a significant decrease in PA levels with maintenance of their circadian rhythmicity. The circadian secretory patterns of PC were similar before and after therapy. In conclusion, long-term treatment with penbutolol appears not only to set BP, PRA and PA values to lower levels, but also to decrease the within-day variation of BP, HR, and PRA. In addition, penbutolol does not influence the 24 h-secretion of PC.
Topics: Administration, Oral; Adult; Aldosterone; Blood Pressure; Circadian Rhythm; Female; Humans; Hydrocortisone; Hypertension; Male; Penbutolol; Propanolamines; Renin
PubMed: 3287810
DOI: No ID Found -
Drug and Chemical Toxicology Mar 1989With a view to examine the effect of chirality and the cause of batch-to-batch variation in the mutagenicity of penbutolol, penbutolol enantiomers - isopenbutolol...
With a view to examine the effect of chirality and the cause of batch-to-batch variation in the mutagenicity of penbutolol, penbutolol enantiomers - isopenbutolol [R(+)-enantiomer] and penbutolol [S(-)-enantiomer] - and two batches of Betapressin were tested employing the Ames Salmonella tester strain TA98. The mutagenic activity of R(+)-enantiomer was found to be similar to that of a batch of penbutolol with a high content of this optical isomer. The pharmaceutical form of penbutolol, Betapressin, exhibited either less or equal mutagenic effectiveness to the S(-)-enantiomer. In the presence of the S9 mix, the mutagenicity of R(+)-enantiomer was only slightly affected in the low dose range of 40 to 160 micrograms/plate. A metabolite of penbutolol, (RS) l"-dehydropenbutolol, did not cause an increase in the number of revertants/plate.
Topics: Animals; Chromatography, High Pressure Liquid; In Vitro Techniques; Mutagenicity Tests; Mutagens; Penbutolol; Propanolamines; Rats; Salmonella typhimurium; Stereoisomerism
PubMed: 2653789
DOI: 10.3109/01480548908999145 -
European Journal of Clinical... 1986A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days. The plasma levels of unmetabolized penbutolol...
A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days. The plasma levels of unmetabolized penbutolol showed a slight but non-significant increase. The biphasic elimination kinetics of penbutolol (half-lives 0.8 and 17 h) was not affected by coadministration of cimetidine. Plasma levels of penbutolol were not significantly altered by chronic treatment with cimetidine, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced.
Topics: Adult; Cimetidine; Drug Interactions; Glucuronates; Heart Rate; Humans; Kinetics; Penbutolol; Physical Exertion; Propanolamines; Time Factors
PubMed: 3956561
DOI: 10.1007/BF00635892 -
Arzneimittel-Forschung Nov 1987The metabolites of 1-tert.-butylamino-3-(2-cyclopentylphenoxy)propan-2-ol (penbutolol Betapressin) penbutolol 2-glucuronide, 4'-OH-penbutolol 2-glucuronide,...
The metabolites of 1-tert.-butylamino-3-(2-cyclopentylphenoxy)propan-2-ol (penbutolol Betapressin) penbutolol 2-glucuronide, 4'-OH-penbutolol 2-glucuronide, 4'-OH-penbutolol 4'-sulfate and 1''-dehydropenbutolol 2-glucuronide were isolated from the urine of patients, purified by high-performance liquid chromatography and characterised by 1H-NMR and mass spectroscopy. Penbutolol 2-glucuronide and 4'-OH-penbutolol 4'-glucuronide were synthesised in vitro from penbutolol and 4'-OH-penbutolol, respectively, using glucuronyltransferase.
Topics: Animals; Biotransformation; Cattle; Glucuronates; Humans; In Vitro Techniques; Mass Spectrometry; Penbutolol; Propanolamines; Rabbits; Rats; Sulfates
PubMed: 3440029
DOI: No ID Found -
South African Medical Journal =... Jun 1981Twelve healthy male volunteers participated in an open cross-over study designed to test whether two fixed-dose combination formulations of penbutolol (40 mg) and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Twelve healthy male volunteers participated in an open cross-over study designed to test whether two fixed-dose combination formulations of penbutolol (40 mg) and furosemide (20 mg), an ordinary and a film-coated tablet, are bio-equivalent. Penbutolol capsules (40 mg) and 20 mg furosemide tablets (Lasix; Hoechst) served as reference formulations. The maximum concentration of furosemide was significantly depressed in the case of fixed-dose combinations, reflecting a possible pharmacokinetic interaction between penbutolol and furosemide. However, the area under the concentration versus time curve for furosemide and its cumulative urinary excretion and diuretic effect were not influenced by penbutolol. On the basis of plasma concentration versus time data and urinary parameters, the two fixed-dose formulations are bio-equivalent.
Topics: Adult; Biological Availability; Clinical Trials as Topic; Drug Combinations; Furosemide; Humans; Kinetics; Male; Penbutolol; Propanolamines; Tablets
PubMed: 7015536
DOI: No ID Found -
Postgraduate Medicine Apr 1991Three recent additions to the list of antihypertensive agents have been approved for use as monotherapy or in combination with other drugs. Betaxolol hydrochloride... (Review)
Review
Three recent additions to the list of antihypertensive agents have been approved for use as monotherapy or in combination with other drugs. Betaxolol hydrochloride (Kerlone) maintains its effect for 24 hours, making it a true once-a-day beta blocker. Penbutolol sulfate (Levatol) is as effective as other beta blockers and diuretics. Doxazosin mesylate (Cardura), a selective alpha 1 blocker, also allows once-a-day dosing and has produced favorable changes in lipid profiles. Two new drug delivery systems, one for verapamil hydrochloride (Verelan) and one for extended-release nifedipine (Procardia XL), allow less frequent dosing and may offer other advantages, such as greater compliance and a more tolerable side-effect profile.
Topics: Antihypertensive Agents; Clinical Trials as Topic; Humans; Hypertension
PubMed: 2008405
DOI: 10.1080/00325481.1991.11700892 -
European Journal of Pharmacology Nov 1992Brain 5-HT1A and 5-HT1B receptors are important targets for drug-induced modulation of 5-HT function in vivo. However, very few compounds are available that are...
Brain 5-HT1A and 5-HT1B receptors are important targets for drug-induced modulation of 5-HT function in vivo. However, very few compounds are available that are effective antagonists at 5-HT1 receptors, thus hampering the progress of fundamental as well as clinical research in this area. The present study assessed the usefulness of the beta-adrenolytic agent (-)-penbutolol (and its (+)-counterpart) as a 5-HT1A receptor-blocking agent. The compound was found to counteract, in a stereospecific fashion, not only the behavioural and hypothermic but also the in vivo 5-HT synthesis/turnover-reducing effects of the specific 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). These findings indicate that (-)-penbutolol is an antagonist at both postsynaptic receptors and somatodendritic autoreceptors of the 5-HT1A subtype. Thus, (-)-penbutolol represents a useful addition to the array of pharmacological tools available for the study of central 5-HT1 receptor-mediated functions.
Topics: 5-Hydroxytryptophan; 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Behavior, Animal; Body Temperature; Brain Chemistry; In Vitro Techniques; Male; Penbutolol; Rats; Rats, Sprague-Dawley; Reserpine; Serotonin; Serotonin Antagonists; Stereoisomerism
PubMed: 1468487
DOI: 10.1016/0014-2999(92)90471-f -
Arzneimittel-Forschung 1983The effect of penbutolol (Betapressin), a stereospecific beta-adrenergic antagonist, on the pharmacokinetics of a single dose of intravenous lidocaine was evaluated in...
The effect of penbutolol (Betapressin), a stereospecific beta-adrenergic antagonist, on the pharmacokinetics of a single dose of intravenous lidocaine was evaluated in seven healthy volunteers. Subjects received a single 100-mg lidocaine intravenous dose of lidocaine hydrochloride, once in the control state and a second time during coadministration of penbutolol, 60 mg daily. Lidocaine volume of distribution was significantly increased during penbutolol treatment (4.9 vs 3.4 l/kg, p less than 0.005), resulting in a significant prolongation of elimination half-life (2.5 vs 2.0 h, p less than 0.025). The mechanism of the distributional shift is not established, but may result from a change in the pattern of peripheral blood flow and therefore the profile of tissue uptake of lidocaine. Total metabolic clearance of lidocaine, however, was not significantly altered by penbutolol (23.0 vs 19.4 ml/min/kg). The present study of healthy volunteers suggests that penbutolol increases lidocaine volume of distribution. If the finding also applied to patients, a higher loading dose of lidocaine might be necessary.
Topics: Adult; Drug Interactions; Half-Life; Humans; Kinetics; Lidocaine; Male; Penbutolol; Propanolamines
PubMed: 6686773
DOI: No ID Found