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Mutation Research Apr 1988Sixteen beta-adrenergic receptor blockers were screened for their mutagenic potential using Salmonella typhimurium strains TA98 and TA100. All except penbutolol were...
Sixteen beta-adrenergic receptor blockers were screened for their mutagenic potential using Salmonella typhimurium strains TA98 and TA100. All except penbutolol were found to be nonmutagenic. Penbutolol was cytotoxic to human fibroblasts and Chinese hamster V79 cells. These effects could be due to its ability to induce DNA-strand breaks detected by hydroxyapatite chromatography, which remained unrepaired within 1 h of incubation. Under the same conditions strand-breaking activity of propranolol, timolol and indenolol could not be detected. Three potential impurities of penbutolol were ineffective in causing DNA-strand breakage and one metabolite of this drug was found to be nonmutagenic.
Topics: Adrenergic beta-Antagonists; Animals; Cell Survival; Cells, Cultured; Cricetinae; DNA Damage; Dose-Response Relationship, Drug; Humans; In Vitro Techniques; Mutagenicity Tests; Mutation; Penbutolol; Propanolamines; Salmonella typhimurium
PubMed: 2895424
DOI: 10.1016/0165-1218(88)90072-9 -
Drug Delivery Jan 2009Iontophoretic transport of penbutolol sulfate across porcine ear skin was studied. Passive transdermal flux of the drug in phosphate-buffered saline was 7.65...
Iontophoretic transport of penbutolol sulfate across porcine ear skin was studied. Passive transdermal flux of the drug in phosphate-buffered saline was 7.65 microg/cm(2) hr. There was statistically significant flux enhancement when direct current iontophoresis was applied. Iontophoresis (0.11 mA/cm(2), 0.17 mA/cm(2), and 0.22 mA/cm(2)) for 6 hr, resulted in net transport of 87.36 microg/cm(2), 137.51 microg/cm(2), and 201.12 microg/cm(2) of penbutolol sulfate, respectively. After 24 hr, cumulative amount of penbutolol transported were 201.63, 300.76, and 359.98 microg/cm(2), respectively. There was a 2.20- (0.11 mA/cm(2)), 3.26- (0.17 m/Acm(2)), and 4.28-fold (0.22 mA/cm(2)) enhancement in transcutaneous steady-state flux values compared to passive delivery. Steady-state fluxes of penbutolol sulfate also increased proportionally to current density. Steady-state fluxes calculated from the linear portion of the cumulative amount versus time curves for penbutolol sulfate were 16.68, 24.97, and 32.76 microg/cm(2)/hr at current densities of 0.11, 0.17, and 0.22 mA/cm(2). This study provides initial evidence for the potential use of iontophoresis for enhanced transdermal delivery of penbutolol sulfate.
Topics: Administration, Cutaneous; Adrenergic beta-Antagonists; Animals; Biological Transport; Drug Delivery Systems; In Vitro Techniques; Iontophoresis; Penbutolol; Skin Absorption; Swine; Time Factors
PubMed: 19555303
DOI: 10.1080/10717540802396976 -
Cancer Chemotherapy and Pharmacology 1994The effect of in vitro treatment of serum with the alkylating agents carmustine (BCNU) and mechlorethamine on the protein binding of penbutolol, a basic agent mainly...
The effect of in vitro treatment of serum with the alkylating agents carmustine (BCNU) and mechlorethamine on the protein binding of penbutolol, a basic agent mainly bound to alpha 1-acid glycoprotein (AAG), was investigated. The free fraction of penbutolol increased significantly (P < 0.001) after the treatment of serum with BCNU (5.27+ +/- 0.47%) and with mechlorethamine (5.23% +/- 0.17%), being 1.98% +/- 0.18% in serum not treated with BCNU or mechlorethamine. In addition, after incubation with BCNU (2 h), the free fraction of penbutolol continued increasing (10.96% +/- 0.70% vs 5.27% +/- 0.47% at time 0; P < 0.001), whereas it remained unchanged after incubation with mechlorethamine. Moreover, dialysis against saline for 24 h did not restore the free fraction of penbutolol, which increased after treatment with carmustine (9.05% +/- 1.24% vs. 11.04% +/- 1.55%, nondialyzed). We concluded that the treatment of cancer patients with alkylating agents could alter the serum proteins and modify their binding capacity, and this should be taken into account in the simultaneous treatment of these patients with other basic drugs like penbutolol, e.g., methadone.
Topics: Adult; Alkylating Agents; Blood Proteins; Carmustine; Dialysis; Drug Interactions; Female; Humans; Male; Mechlorethamine; Penbutolol; Protein Binding
PubMed: 8174208
DOI: 10.1007/BF00686119 -
Pharmatherapeutica 1985A double-blind study was carried out in two parallel groups of patients with mild to moderate hypertension to assess the efficacy and tolerance of the combination 20 mg... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A double-blind study was carried out in two parallel groups of patients with mild to moderate hypertension to assess the efficacy and tolerance of the combination 20 mg penbutolol plus 3 mg piretanide in comparison to 40 mg penbutolol alone over a period of 6 weeks. Active drug treatment in the 51 patients studied was preceded by a 2-week period of placebo. The results showed that in both groups there was an effective reduction in systolic and diastolic blood pressure compared with initial levels. Although there was no significant difference between the groups, the normalization of diastolic blood pressure (less than 95 mmHg) was achieved in 70% of the patients receiving the combination and in 59% of the patients treated with penbutolol alone. Pulse rate decreased in both groups, body weight only in the combination group. The biochemical and haematological parameters showed no clinically relevant changes during treatment with either drug regimens. Minor side-effects definitely or probably associated with the treatment were observed in both groups but were generally mild and did not interfere with treatment. No patient withdrew prematurely from the trial.
Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Penbutolol; Propanolamines; Random Allocation; Sulfonamides; Time Factors
PubMed: 3903788
DOI: No ID Found -
Journal of Clinical Pharmacology Jul 1979
Topics: Adult; Aged; Blood Pressure; Humans; Hypertension; Middle Aged; Penbutolol; Placebos; Propanolamines; Renin
PubMed: 479383
DOI: 10.1002/j.1552-4604.1979.tb02495.x -
Research Communications in Molecular... Apr 1996The pharmacokinetic and pharmacodynamic profiles of penbutolol were examined in healthy volunteers and in cancer patients using a pharmacokinetic/pharmacodynamic (pk/pd)...
The pharmacokinetic and pharmacodynamic profiles of penbutolol were examined in healthy volunteers and in cancer patients using a pharmacokinetic/pharmacodynamic (pk/pd) model. After receiving a 40 mg single oral dose of penbutolol, the absorption rate constant, apparent volume of distribution and serum clearance of penbutolol were found to be reduced in the cancer group. Changes in the disposition of the conjugate metabolite were also observed in the cancer patients. Penbutolol unbound fraction in serum was statistically decreased (p < 0.005) in the cancer group, according to the increase in the serum levels of alpha 1-acid glycoprotein seen in that group (p < 0.05). The pharmacodynamic effect of penbutolol was measured as the reduction in heart rate (HR); in healthy volunteers, a linear relationship (p < 0.01) between effect and penbutolol serum concentrations (total or unbound) was found. In contrast, in cancer patients, values of HR did not vary statistically in respect to baseline values. These results show that in cancer patients, a change in the pharmacokinetics of penbutolol occurs (associated with changes in drug protein binding), together with an alteration in the pharmacodynamics.
Topics: Adult; Aged; Binding, Competitive; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Penbutolol; Protein Binding
PubMed: 8733828
DOI: No ID Found -
Annals of Clinical Research Apr 1978The antihypertensive effect of a new non-selective beta-adrenergic blocking compound, penbutolol (40 mg b.i.d.), was compared with propranolol (160 mg b.i.d.) in a... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The antihypertensive effect of a new non-selective beta-adrenergic blocking compound, penbutolol (40 mg b.i.d.), was compared with propranolol (160 mg b.i.d.) in a series of 20 hypertensive patients using a double-blind cross-over scheme. Both compounds reduced both the supine and the standing blood pressure significantly. The magnitude of the responses did not differ significantly and both compounds evoked a commensurate decrease in heart rate. No significant side-effects were noted and a series of laboratory tests did not disclose any biochemical changes.
Topics: Adrenergic beta-Antagonists; Adult; Clinical Trials as Topic; Cyclopentanes; Double-Blind Method; Drug Evaluation; Female; Humans; Hypertension; Male; Middle Aged; Posture; Propanolamines; Propranolol
PubMed: 28071
DOI: No ID Found -
Clinical Pharmacology and Therapeutics Jun 1977The relative potency of penbutolol, a new beta adrenergic receptor blocking agent, was compared with propranolol by a four-point assay on healthy male subjects. A... (Comparative Study)
Comparative Study
The relative potency of penbutolol, a new beta adrenergic receptor blocking agent, was compared with propranolol by a four-point assay on healthy male subjects. A dose-response relationship to intravenous doses of propranolol in the microgram range was obtained during a steady state of infusion of epinephrine. Two subjects underwent the entire assay according to the Latin square design and four others each underwent one schedule of design on different days. The potency of penbutolol thus assessed was consistent with reported results. This study emphasizes the importance of intersubject variation and differential receptor sensitivity in individuals. The use of epinephrine as a beta receptor adrenergic agonist for evaluation of selective beta adrenergic receptor blocking activities is discussed.
Topics: Adrenergic beta-Antagonists; Adult; Blood Pressure; Cyclopentanes; Dose-Response Relationship, Drug; Epinephrine; Humans; Male; Propanolamines; Propranolol
PubMed: 16716
DOI: 10.1002/cpt1977216685 -
Journal of Clinical Pharmacology Apr 1977Plasma levels of penbutolol (HOE 893d) were determined in eight healthy adult male subjects after oral administration of 50-mg capsules. Fast absorpiton of the drug from...
Plasma levels of penbutolol (HOE 893d) were determined in eight healthy adult male subjects after oral administration of 50-mg capsules. Fast absorpiton of the drug from the gastrointestinal tract was indicated by the rapid increase in plasma levels during the absorption phase, with a peak time at about 1 hour after dosing in all subjects. After the peak level, plasma concentrations declined biexponentially, with an average half-life of 2.5 and 27 hours for the fast and slow disposition phases, respectively. These values were in good agreement with data previously found for this drug. Cumulative excretion of intact drug in the urine of the eight subjects during 72 hours after dosing was less than 4 per cent, except for one subject who excreted 9.82 per cent of the dose. Large individual variations were found for area under the plasma level curves, disposition rates, and amounts of intact drug excreted in the urine. Significant pharmacologic effects were noted in all eight subjects at the 50-mg dose level, and mild side effects were evident in one half of these subjects. The average drop in blood pressure and pulse rate for all subjects was 26/18 mm Hg and 19 beats per minute, respectively.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Blood Pressure; Cyclopentanes; Humans; Kinetics; Male; Propanolamines; Pulse; Spectrometry, Fluorescence; Time Factors
PubMed: 14976
DOI: 10.1177/009127007701700407 -
The Medical Journal of Australia Jan 1980The hypotensive effect of penbutolol, a new beta-adrenergic blocking drug, has been evaluated in a doulbe-blind crossover trial on 15 patients. Blood pressures were... (Clinical Trial)
Clinical Trial
The hypotensive effect of penbutolol, a new beta-adrenergic blocking drug, has been evaluated in a doulbe-blind crossover trial on 15 patients. Blood pressures were significantly lower during active drug treatment (P less than 0.001), the average reduction being: 1.7/0.9 kPa (13/7 mmHg) erect.
Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Penbutolol; Propanolamines
PubMed: 6987484
DOI: No ID Found