Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Penbutolol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group.

Dose-response relations with penbutolol--a beta-adrenergic blocking agent--were evaluated in a double-blind multiclinic study conducted in 302 outpatients with mild to moderate hypertension (untreated supine diastolic blood pressure [BP] greater than or equal to 95 and less than or equal to 115 mm Hg). Penbutolol was administered once daily in 10, 20 or 40 mg doses for 6 weeks and compared with placebo. Mean declines from baseline in supine diastolic BP were comparable in the 3 penbutolol treatment groups and significantly superior to placebo (p less than 0.05). A significant difference between penbutolol dosage groups was observed only for supine systolic BP; the mean decline at 20 mg/day was significantly larger than that at 10 mg/day (p less than 0.05). Maximum BP response developed in approximately 4 weeks at 10 mg/day and in 2 weeks at the higher dosages. Decline in mean heart rate after 6 weeks of penbutolol therapy significantly exceeded placebo only at 40 mg/day (7.2 vs 2.5 beats/min, p less than 0.05). Treatment was well-tolerated and discontinued because of adverse effects in only 7 patients receiving penbutolol and 3 receiving placebo. The lack of significant bradycardia and the low incidence of other troublesome adverse effects are potential advantages during antihypertensive therapy with penbutolol. With rapid onset of effect and good efficacy and tolerability, the 20 mg once-daily dose appears to be optimum for therapy with this new agent.

Blood Pressure↗
PubMed1982

Efficacy of penbutolol and a fixed combination of penbutolol with furosemide in the treatment of hypertension.

In an open multi-centre study, 51 patients with mild to moderate hypertension were treated with either a single dose of 40 mg penbutolol per day for 8 weeks or changed over at 4 weeks due to inadequate response with penbutolol alone to a single dose (1 tablet) of a fixed combination of 40 mg penbutolol and 20 mg furosemide per day for a further 4 weeks. Thirty-six (70%) of the patients showed an adequate reduction in diastolic blood pressure to 95 mmHg or less on penbutolol alone. Of the 15 patients who did not show the desired response to penbutolol alone, 13 (86.7%) showed a satisfactory reduction in blood pressure after 4 weeks on the combination product; 2 of these patients had received 1 tablet twice daily from Week 6 of treatment. Two other patients received 1 tablet of the combination twice daily from Week 8 onwards for 2 weeks. Only 1 of them did not respond to this therapy. Blood pressure reduction and weight loss were significantly greater on the combination product than on penbutolol alone. No clinically significant changes were noted in serum potassium, glucose, creatinine or uric acid levels, and mild gastric side-effects at the beginning of treatment were reported in only 3 patients, 1 of whom was also receiving indomethacin.

Adult↗
PubMed1985

Efficacy of penbutolol and a combination of a low dose of penbutolol with piretanide in the treatment of mild to moderate hypertension.

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.

Adult↗
PubMed1986

Pharmacokinetics and dynamics of penbutolol in humans: evidence for pathway-specific stereoselective clearance.

The pharmacokinetics and dynamics of the D- and L-isomers of the beta-adrenergic blocking agent penbutolol were investigated in healthy human volunteers. In Study One, subjects received a single 40-mg oral dose of L-penbutolol (the pharmacologically active stereoisomer), and matching placebo on two occasions. A mean peak serum penbutolol concentration of 268 ng/ml was reached at 0.9 h after dosing. Elimination half-life averaged 1.6 h, and total clearance 16.6 ml/min per kg body weight. Changes in blood pressure, ventricular rate, and rate of circumferential fiber shortening (Vcf) did not differ between L-penbutolol and placebo. In Study Two, subjects received 40 mg D-penbutolol, L-penbutolol, and placebo on three occasions. Total clearance of D-penbutolol was higher than for the L-isomer (43.7 vs 15.9 ml/min/kg; P less than 0.01); this was reflected in correspondingly increased area under the serum concentration curve for conjugates of the oxidized metabolite 4-hydroxy penbutolol (2.25 vs 0.66 micrograms/ml X h; P less than 0.005). In contrast, direct conjugates of L-penbutolol achieved higher serum concentrations than conjugates of D-penbutolol. Alterations in blood pressure, ventricular rate, and Vcf for D-penbutolol, L-penbutolol, and placebo were quantitatively small. Thus the clearance of penbutolol after oral administration in humans is stereoselective, but the oxidative pathway is more stereosensitive than the parallel conjugative pathway. Penbutolol causes minimal alterations in parameters of cardiac function after single 40-mg doses in healthy humans.

Administration, Oral↗
PubMed1988

Penbutolol: pharmacokinetics, effect on exercise tachycardia, and in vitro inhibition of radioligand binding.

The pharmacokinetics of penbutolol 40 mg, its reduction in exercise-induced tachycardia, and the in vitro inhibition of radioligand binding to beta-adrenoceptors by plasma have been investigated in 7 healthy volunteers. The peak penbutolol concentration of 285 ng/ml was observed 1.2 h after administration, and the maximum of 4'-OH-penbutolol of 4.76 ng/ml was found after 1.64 h. Penbutolol was detected for up to 48 h, and 4'-OH-penbutolol dropped below the limit of detection after about 10 h. The terminal plasma concentration of penbutolol declined with an average half-life of 19 h. The maximum reduction in exercise-induced tachycardia was 33 beats/min 2.6 h after taking penbutolol. There was still a significant reduction of about 7 beats/min after 48 h. This effect could be adequately explained by the concentration-time course of penbutolol in combination with Clark's model of the concentration-effect relationship. Antagonist activity in plasma caused 91% inhibition of radioligand binding in vitro to beta 2-adrenoceptors on rat reticulocyte membranes 1.6 h after intake of penbutolol. By 48 h after intake, radioligand binding was still significantly inhibited (23%). The in vitro inhibition of radioligand binding by plasma showed a linear correlation with the reduction in exercise-induced tachycardia for all phases of the workload. The time course of the reduction in heart rate was completely explained by the in vitro inhibition of radioligand binding. However, it was not possible to explain the in vitro inhibition of radioligand binding by the concentration-time course of penbutolol using a simple competition model, although both variables were based on the same sampling site. When the in vitro inhibition of radioligand binding was plotted against the penbutolol concentration at the same sampling times (with both variables transformed to multiples of the apparent inhibition constant) the discrepancy became even more apparent as time-related counterclockwise hysteresis. None of the known metabolites of penbutolol can explain the discrepancy between the penbutolol concentration and the inhibition of radioligand binding in vitro. It appears that an other active metabolite is formed, which contributes to the effect in vitro and in vivo and so can explain the observed discrepancy.

Adrenergic beta-Antagonists↗
PubMed1985

Penbutolol: beta-adrenoceptor interaction and the time course of plasma concentrations explain its prolonged duration of action in man.

Beta-adrenoceptor binding of (-) penbutolol and its active metabolite 4-hydroxy-penbutolol to rat reticulocyte membranes was shown in the presence of native human plasma. Due to the high plasma protein binding (approximately 99%) the apparent Ki-values of penbutolol were shifted 100-fold to the right after inclusion of plasma in the assay; the Ki was approximately 40-70 ng/ml. That value is comparable to the IC50-values calculated from clinical studies. The interaction of 4-hydroxy-penbutolol with beta-adrenoceptors was not affected to the same extent by inclusion of plasma protein binding approximately 80%, apparent Ki-value approximately 7 ng/ml. Thus, the active metabolite of penbutolol displays higher potency at beta-adrenoceptors in vitro due to its lesser degree of plasma protein binding. A prediction procedure for antagonist activity after penbutolol administration using beta-adrenoceptor interaction and plasma concentration kinetics suggests that, in addition to a rapid elimination process from human plasma, a slow elimination phase of penbutolol (or an active metabolite) is necessary to explain the long duration of action observed in clinical studies after a single oral dose. Inhibition in vitro of beta-adrenoceptor binding by plasma samples obtained after oral administration of 40 mg penbutolol to 3 healthy volunteers indicated a biphasic concentration-time profile of the antagonist in plasma and was in accordance with the time course of the reported reduction in exercise tachycardia. Finally, plasma concentrations of penbutolol equivalents derived from the receptor assay were in the range of penbutolol concentrations detected by physico-chemical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗
PubMed1990

Absence of genotoxic activity of penbutolol in bacterial and mammalian cell screening systems.

The genotoxic potential of the beta-adrenergic blocker penbutolol was assessed using the Ames and HGPRT tests, unscheduled DNA synthesis (UDS) and alkaline elution assays. In the Ames test, penbutolol was tested for cytotoxicity and genotoxic activity in concentration ranges of 0.8-500 micrograms/plate and 0.1-125 micrograms/ml in the HGPRT, UDS and alkaline elution assays. In the Ames test penbutolol showed significant toxicity above 500 micrograms/plate. In the mammalian cells (V79) used for the HGPRT test and A459 cells used for alkaline elution and UDS assays, penbutolol was cytotoxic at concentrations above 30 micrograms/ml. In another series of experiments, male Wistar rats were treated i.p. with penbutolol (1, 10 and 100 mg/kg) and after 2 h liver nuclei were isolated and formation of single DNA-strand breaks was measured. The results of the present study demonstrate the absence of genotoxic activity of penbutolol in the 5 strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA1538) and in the strain of Escherichia coli WP2 uvrA in the presence or absence of metabolic activation. In V79 cells, penbutolol showed no mutagenic effects at the HGPRT locus in the presence or absence of metabolic activation. Additionally, no significant incorporation of [3H]thymidine into the DNA in the UDS test or formation of DNA-strand breaks in the alkaline elution assay was detected in the non-toxic concentration range of penbutolol with or without metabolic activation. Furthermore, penbutolol did not cause DNA damage in liver nuclei isolated from penbutolol-treated rats.

Animals↗
PubMed1993

In vivo microdialysis evidence for central serotonin1A and serotonin1B autoreceptor blocking properties of the beta adrenoceptor antagonist (-)penbutolol.

Recently, we found that the beta 1/beta 2 adrenoceptor blocking agent (-)penbutolol prevents behavioral and biochemical actions of the specific serotonin (5-HT)1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. The putative 5-HT1 receptor antagonist profile of (-)penbutolol was further explored in the present study, using in vivo microdialysis methods to assess its effects on central 5-HT release. (+)Penbutolol and (-)pindolol were included for comparison purposes. In contrast to (-)pindolol (8.0 mg/kg s.c.), administration of (-)penbutolol (2.0 or 8.0 mg/kg s.c.) increased hippocampal 5-HT output. The (-)penbutolol-induced 5-HT response was dose-related, stereoselective and Ca(++)-dependent. In addition, the 5-HT response to (-)penbutolol was abolished by omitting the 5-HT reuptake blocker citalopram from the perfusion medium, suggesting the need for endogenous 5-HT tone. Local (-)penbutolol (1 microM) perfusion increased the 5-HT output per se, and also blocked 5-HT release suppression caused by the 5-HT1B receptor agonist CP-93,129. Furthermore, (-)penbutolol, but not its (+)antipode, prevented the decrease of 5-HT release induced by the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. By comparison, the 5-HT1 receptor inactive beta adrenoceptor blockers metoprolol (beta 1) and ICI 118,551 (beta 2), given alone or in combination, did not increase 5-HT output and were ineffective in antagonizing the (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin response. The data indicate that (-)penbutolol possesses 5-HT1A and 5-HT1B autoreceptor antagonist properties, and may be a useful tool in studies of central 5-HT receptor-mediated function.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1985

Pharmacokinetics of penbutolol and its metabolites in renal insufficiency.

The pharmacokinetics of penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment. A single oral dose of penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged penbutolol were not altered by renal impairment. The 48 h-urinary excretion of penbutolol and its metabolites reached 13-14% of the administered dose, which is consistent with extensive metabolism of the drug. After treatment for 30 days with penbutolol 40 mg/d there was no accumulation of the parent drug but the concentration of its conjugates was increased. It is concluded that the dose of penbutolol need not be changed in patients with mild renal insufficiency, 4-hydroxypenbutolol is unlikely to participate in the anti-hypertensive effect of the drug, due to its low concentrations, and biotransformation of penbutolol may be enhanced during chronic treatment.

Adult↗
PubMed1999

Effects of (-)-tertatolol, (-)-penbutolol and (+/-)-pindolol in combination with paroxetine on presynaptic 5-HT function: an in vivo microdialysis and electrophysiological study.

The antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) might be enhanced by co-administration of 5-HT1A receptor antagonists. Thus, we have recently shown that the selective 5-HT1A receptor antagonist, WAY 100635, blocks the inhibitory effect of an SSRI on 5-HT cell firing, and enhances its ability to elevate extracellular 5-HT in the forebrain. Here we determined whether the beta-adrenoceptor/5-HT1A receptor ligands (+/-)-pindolol, (-)-tertatolol and (-)-penbutolol, interact with paroxetine in a similar manner. Both (-)-tertatolol (2.4 mg kg(-1) i.v.) and (-)-penbutolol (2.4 mg kg(-1) i.v.) enhanced the effect of paroxetine (0.8 mg kg(-1) i.v.) on extracellular 5-HT in the frontal cortex, whilst (+/-)-pindolol (4 mg kg(-1) i.v.) did not. (-)-Tertatolol (2.4 mg kg(-1) i.v.) alone caused a slight increase in 5-HT however, (-)-penbutolol (2.4 mg kg(-1) i.v.) alone had no effect. In electrophysiological studies (-)-tertatolol (2.4 mg kg(-1) i.v.) alone had no effect on 5-HT cell firing but blocked the inhibitory effect of paroxetine. In contrast, (-)-penbutolol (0.1-0.8 mg kg(-1) i.v.) itself inhibited 5-HT cell firing, and this effect was reversed by WAY 100635 (0.1 mg kg(-1) i.v.). We have recently shown that (+/-)-pindolol inhibits 5-HT cell firing via a WAY 100635-sensitive mechanism. Our data suggest that (-)-tertatolol enhances the effect of paroxetine on forebrain 5-HT via blockade of 5-HT1A autoreceptors which mediate paroxetine-induced inhibition of 5-HT cell firing. In comparison, the mechanisms by which (-)-penbutolol enhances the effect of paroxetine on extracellular 5-HT is unclear, since (-)-penbutolol itself appears to have agonist properties at the 5-HT1A autoreceptor. Indeed, the agonist action of (+/-)-pindolol at 5-HT1A autoreceptors probably explains its inability to enhance the effect of paroxetine on 5-HT in the frontal cortex. Overall, our data suggest that both (-)-tertatolol and (-)-penbutolol are superior to (+/-)-pindolol in terms of enhancing the effect of an SSRI on extracellular 5-HT. Both (-)-tertatolol and (-)-penbutolol are worthy of investigation for use as adjuncts to SSRIs in the treatment of major depression.

Adrenergic beta-Antagonists↗
PubMed1987

Isolation, identification and in vitro synthesis of conjugates of penbutolol and its metabolites.

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.

Animals↗
PubMed1980

[On the pharmacology of the beta-receptor blocker penbutolol (author's transl)].

1-tert.-Butylamino-3-(2-cyclopentylphenoxy)-propan-2-ol (penbutolol, Hoe 893d) is a beta-adrenergic blocking agent about 4 times more active than propranolol in vivo and in vitro. In comparison to propranolol it is characterized by a longer lasting activity. The antihypertensive effect of penbutolol in spontaneously hypertonic rats is more than 5 times stronger than that of propranolol. Penbutolol reduces basal plasma renin activity in the same dose range as does propranolol but is about 3 times stronger with respect to isoproterenol-induced increase of PRA. Penbutolol is 5 times more potent than propranolol inhibiting isoproterenol-stimulated phosphorylase activity in the isolated heart. In reserpine pretreated rats, penbutolol has a moderate intrinsic sympathomimetic activity (ISA). Penbutolol shows less unspecific actions -- such as negative inotropy or calcium antagonism -- than propranolol. Characteristic parameters of lung function (compliance and resistance) are less affected by penbutolol than propranolol in spite of the fact that penbutolol has a stronger beta-adrenergic blocking effect.

Animals↗
PubMedDate not supplied

Plasma protein binding of penbutolol in pregnancy.

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.

Adult↗
PubMed1989

Effects of penbutolol on plasma atrial natriuretic peptide and antidiuretic hormone levels before and after exercise: a double-blind comparison against placebo.

A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) levels before and after exercise. Each subject underwent several bicycle ergometric exercises lasting 6 min before and after the application of test medications. Ergometric exercises were performed before medication, and at 2, 5, 9 and 24 hours after medication. Blood samples for ANP and ADH levels were drawn before, after 15 min, after 2 hours (immediately after ergometry) and 5, 7, 9, and 24 hours after medication (immediately before ergometry). Urine was collected as follows: -2 to 0, 0 to 2, 2 to 4, 4 to 7, 7 to 14 and 14 to 24 hours after medication, and the volume as well as sodium excretion were documented. Penbutolol caused suppression of the exercise-induced increase in ANP. The 2 to 4 hour fractional sodium excretion was significantly decreased from 12.1 +/- 4.9 mmol/fraction after placebo treatment to 7.8 +/- 3.0 mmol/fraction after penbutolol application (p less than 0.03). There were no differences in the urinary outputs between penbutolol and placebo until 4 hours after medication, but penbutolol caused the total urinary output to increase from 1390 +/- 388 ml/24 hr during placebo treatment to 1725 +/- 549 ml/24 hr (p less than 0.02) due to the last collection fraction. Blood pressure and pulse rate both decreased during exercise after penbutolol. As opposed to the suppressing influence of penbutolol on ANP, ADH plasma levels were increased after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

[Modification of myocardial function parameters by L- and D-penbutolol--an echocardiography, placebo-controlled double-blind study].

In order to study left ventricular contraction parameters of L-penbutolol and D-penbutolol (isopenbutolol) we evaluated TM-echocardiograms of 12 healthy volunteers at 30 and 60 minute intervals for 8 hours after oral administration of 40 mg L- and D-penbutolol and placebo. Three different observers determined end-systolic and end-diastolic dimensions, left ventricular shortening fraction (SF) as well as mean-, peak- and rate corrected circumferential fiber shortening (VCF) and calculated at each measuring point the difference from the control value (Delta). L-penbutolol demonstrated a typical beta-blocking effect with a significant (p less than 0.001) decrease of systolic (11.1 +/- 8.6 mm Hg) and diastolic blood pressure (6.7 +/- 4.6 mm Hg) and heart rate (10.0 +/- 7.4 bpm) as well as a significant (p less than 0.001) negative inotropic effect expressed by a decrease of SF (6.5 +/- 4.2%) and VCF-mean (0.40 +/- 0.15 circ/s), VCF-peak (1.04 +/- 0.61 circ/s) and rate corrected VCF (0.28 +/- 0.08 circ/s). However, we saw a similar but less distinct negative inotropic and chronotropic effect of D-penbutolol as compared to placebo. HR decreased by 5.3 +/- 6.2 bpm (p less than 0.001), SF decreased maximally by 5.0 +/- 3.2% (p less than 0.05), VCF-mean by 0.27 +/- 0.08 circ/s (p less than 0.001), VCF-peak by 0.71 +/- 0.31 circ/s (p less than 0.001) and rate corrected VCF by 0.22 +/- 0.04 circ/s (p less than 0.001). By means of TM echocardiography it was therefore possible to document a strong beta-blocking effect of L-penbutolol as well as a negative inotropic and negative chronotropic effect by the D-isomer of penbutolol.

Adult↗
PubMed1996

Pharmacokinetics and pharmacodynamics of penbutolol in healthy and cancer subjects: role of altered protein binding.

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.

Adult↗
PubMed1975

Long term treatment of moderate hypertension with penbutolol (Hoe 893d). I. Effects on blood pressure, pulse rate, catecholamines in blood and urine, plasma renin activity and urinary aldosterone under basal conditions and following exercise.

The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2-4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3-8 months) 4-60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2-4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20-30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.

Adrenergic beta-Antagonists↗
PubMed1980

Single daily dose penbutolol in the treatment of hypertension: a double blind crossover comparison with propranolol.

Penbutolol is a potent long-acting non-cardioselective beta-adrenergic blocker with partial agonist activity. A double-blind cross-over comparison of penbutolol given in a single daily dose and propranolol given twice daily in the treatment of ambulant patients with moderate hypertension is described. Fourteen patients completed the study and were treated with each drug for 12 weeks. Penbutolol in daily doses of 20-120 mg and propranolol in daily doses of 80-400 mg produced similar significant reductions in both supine and erect blood pressure. Penbutolol did not reduce heart rate to the same extent as propranolol, in equivalent doses. Penbutolol appears to produce adequate control of moderate hypertension when administered once a day, and this effect appears to be equivalent to divided doses of propranolol. No serious adverse effects were reported, although one patient receiving penbutolol experienced severe eye pains at a dose of 40 mg which resolved on crossing over to treatment with propranolol.

Adult↗