DETERMINATION OF SOTALOL, OXPRENOLOL AND LABETALOL IN BINARY MIXTURES AND IN SPIKED HUMAN SERUM BY DERIVATIVE SPECTROPHOTOMETRIC METHOD.Acta Poloniae Pharmaceutica Jan 2017The usefulness of derivative spectrophotometry for the determination of labetalol, sotalol and oxprenolol in binary mixtures and in human spiked serum was checked. To...
The usefulness of derivative spectrophotometry for the determination of labetalol, sotalol and oxprenolol in binary mixtures and in human spiked serum was checked. To this aim a spectrophotometric analysis of samples in the UV range was carried out and the obtained results revealed that derivative spectropho- tometry allows for the fast, accurate and precise determination of the tested substances in spite of their clear interference in the zero-order spectra. For quantitative determinations "zero-crossing" technique was used to establish wavelengths for zeros of specified component. In a mixture of labetalol and oxprenolol the following wavelengths were established: D1 λ = 245.32 nm and 266.03 nm, D2 λ = 243.30 nm and 301.09 nm. respectively. D3 derivative did not show zeros suitable for quantitative analysis. For the analysis of labetalol and sotalol mixture, D3 derivative spectrophotometry was used at the following wavelengths: = 246.03 nm and λ = 249.91 rum, respectively. In this case, the curves of Dl and D2 derivatives showed no zeros that can be used in quantitative analysis. To determine the concentration of the components in a mixture containing oxprenolol and sotalol the following wavelengths were selected: for oxprenolol DI λ = 245.32 nm, D2 λ = 240.18 run, D3 λ = 232.05 nm and for sotalol Dl λ = 230.56 nm, D2 Xλ= 232.65 nm and D3 X = 238.84 tm, respectively. The developed spectrophotometric method was characterized by high sensitivity and accuracy, LOD determined for sotalol was in the range of 0.21-1.88 μg/mL, for labetalol 1.00-3.43 μg/mL and for oxprenolol 0.16-2.06 μg/mL; LOQ determined for sotalol was in the range of 0.65-5.70 μg/mL, for labetalol 3.11-10.39 μg/mL and for oxprenolol 0.47-6.23 μg/mL, depending on the composition of the tested mixture and the order of the deriv- ative. The recovery of the individual components was within the range of 100 ± 5%. The linearity range was wide and estimated for sotalol in the range of 11.00-38.50 μg/mL, for labetalol 12.80-44.80 μg/mL and for oxprenolol 12.60-44.10 μg/mL with correlation coefficients in the range of 0.9977-0.9999.
Topics: Humans; Labetalol; Limit of Detection; Oxprenolol; Sotalol; Spectrophotometry, Ultraviolet
Acta Poloniae PharmaceuticaThe kinetics of hydrolysis of octanoyl ester of oxprenolol (O-OXP) and benzoyl ester of oxprenolol (Benz-OXP) has been investigated in aqueous solution at 310 K over the...
The kinetics of hydrolysis of octanoyl ester of oxprenolol (O-OXP) and benzoyl ester of oxprenolol (Benz-OXP) has been investigated in aqueous solution at 310 K over the pH range 0.42-9.5. The decomposition was followed by UV spectral method. At the pH range 0.42 to 9.5, hydrolysis of oxprenolol esters (E-OXP) consists of hydrolysis of BH+ molecules catalyzed by hydrogen ions, spontaneous hydrolysis of BH+ molecules and hydrolysis of BH+ and B molecules catalyzed by hydroxide ions. Various buffer substances were found to exhibit general acid and base catalysis of the degradation.
Topics: Adrenergic beta-Antagonists; Chemical Phenomena; Chemistry, Physical; Colorimetry; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Magnetic Resonance Spectroscopy; Oxprenolol; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet
A study of the relationship between the structure of homologous series of oxprenolol at various pH values.Acta Poloniae PharmaceuticaStability of series of O-acyl esters of oxprenolol prepared as potential pro-drugs, is investigated over the pH range 0.4-10 at 37 degrees C. Maximum stability of all...
Stability of series of O-acyl esters of oxprenolol prepared as potential pro-drugs, is investigated over the pH range 0.4-10 at 37 degrees C. Maximum stability of all esters occurred at pH 3-4. The most stable derivative was found to be pivaloyl ester. The relationship between Charton Steric parameters (v) and the catalytic rate constant of hydrolysis is investigated.
Topics: Adrenergic beta-Antagonists; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Oxprenolol
Acta Poloniae PharmaceuticaThe stability of each O-acyl derivative was investigated in a solution of hydrochloric acid, artificial gastric juice, phosphate buffer at pH 7.4 and in artificial...
The stability of each O-acyl derivative was investigated in a solution of hydrochloric acid, artificial gastric juice, phosphate buffer at pH 7.4 and in artificial intestinal juice. A study of the relationship between the structure and enzymatic hydrolysis of the homologous series of oxprenolol esters was made.
Topics: Esters; Gastric Juice; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Magnetic Resonance Spectroscopy; Oxprenolol; Spectrophotometry, Ultraviolet
British Journal of Clinical Pharmacology May 19881. Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
1. Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2. Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P less than 0.001), but differences were slight. 3. Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4. The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.
Topics: Adult; Electrocardiography; Exercise Test; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxprenolol
Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.British Journal of Clinical Pharmacology Sep 19871 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were...
1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxprenolol was absorbed in the jejunum and 48% in the ileum; the differences were significant. 3 The plasma concentration-time profiles were similar for the two perfusions. The AUC and Cmax values of free and conjugated oxprenolol for the jejunal perfusion were significantly lower than those of ileum. They showed large but consistent intersubject variations in the two treatments. 4 Study II investigated, using the same technique, the influence of nutrients and digestive secretions on jejunal absorption and systemic availability of this drug. A saline (in treatments A and B) or a nutrient (in treatment C) solution containing oxprenolol was perfused into the jejunum below a balloon either inflated (A) or deflated (B and C). 5 The disappearance rate of oxprenolol from the jejunum was unaffected by endogenous secretions. The mean amount of drug absorbed along a 30-cm jejunal segment accounted for 52 (A) and 57% (B) of the total amount perfused. The intestinal absorption rate was markedly increased in the presence of nutrients (mean amount absorbed 96% for C). 6 The change in the rate of disappearance from the intestine had no effect on the systemic availability of oxprenolol (mean AUC values 8740, 8250 and 8020 nmol l-1 h for A, B and C, respectively) or its elimination from plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Biological Availability; Food; Humans; Ileum; Intestinal Absorption; Intestinal Secretions; Jejunum; Male; Oxprenolol; Perfusion
Single-dose pharmacokinetic and pharmacodynamic comparison of polymer-matrix (Slow Trasicor) and Oros dosage forms of oxprenolol in healthy volunteers.British Journal of Clinical Pharmacology 1985Oxprenolol was administered in single doses by mouth to healthy volunteers either in a polymer-matrix slow-release formulation (Slow Trasicor) or in osmotic... (Comparative Study)
Oxprenolol was administered in single doses by mouth to healthy volunteers either in a polymer-matrix slow-release formulation (Slow Trasicor) or in osmotic drug-delivery systems (oxprenolol Oros). Plasma oxprenolol concentrations and heart rates after exercise were measured. Plasma concentrations of the drug were maximal at 3 h but negligible at 24 h after administration of Slow Trasicor. Following ingestion of the Oros systems measurable concentrations were maintained throughout 24 h. Significant reduction of exercise-induced tachycardia persisted for 24 h after administration of oxprenolol Oros. With Slow Trasicor heart rate responses had returned to baseline values by this time. The osmotic drug-delivery systems appear to sustain significant beta-adrenoceptor blockade for 24 h after a single oral dose.
Topics: Adult; Delayed-Action Preparations; Female; Heart Rate; Humans; Kinetics; Male; Oxprenolol; Physical Exertion
Comparison of the beta-adrenoceptor blocking activity of oxprenolol, slow release oxprenolol and a combined oxprenolol diuretic preparation.British Journal of Clinical Pharmacology Dec 19811 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol,... (Clinical Trial)
Clinical Trial Comparative Study
1 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg slow release oxprenolol with 0.25 mg cyclopenthiazide and placebo. Blood samples were obtained before and at 1, 2, 3, 6, 8, 12 and 24 h after drug administration and assayed for oxprenolol concentration. 2 The three formulations produced maximum reductions of 29% in the exercise tachycardia 3 to 6 h after drug administration. At 24 h the effects of the three preparations were not significantly different from placebo. 3 There were no significant differences in the plasma concentrations produced by the three formulations during the 24 h period. 4 These observations suggest that the slow release formulations of oxprenolol should be given twice daily to maintain cardiac beta-adrenoceptor blockade throughout a period of 24 h.
Topics: Adrenergic beta-Antagonists; Adult; Cyclopenthiazide; Delayed-Action Preparations; Drug Combinations; Heart Rate; Humans; Male; Oxprenolol; Physical Exertion; Time Factors
Clinical Pharmacology and Therapeutics Jun 1980Oxprenolol is an experimental beta adrenergic blocker with intrinsic sympathomimetic activity. To compare the effects of long-term administration of oxprenolol on... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Oxprenolol is an experimental beta adrenergic blocker with intrinsic sympathomimetic activity. To compare the effects of long-term administration of oxprenolol on hypertension and hemodynamics with the effects of propranolol, 20 patients with essential hypertension were divided in a double-blind random manner into two 10-patient groups and given placebo for 2 wk, followed by equipotent doses of oxprenolol or propranolol for 5 wk and by placebo for another 2 wk. Right heart cardiac catheterization was performed at the beginning and at the end of the 5-wk beta blockade. Heart rates and blood pressures fell markedly with both agents, although standing heart rate was lowered more by propranolol than by oxprenolol. Plasma renin activity was much lower after beta blockade with either drug. There was no correlation between decreases in blood pressure and renin activity. Although during the stress of repeat cardiac catheterization heart rates remained significantly lower than control, the intra-arterial pressures were not altered significantly by oxprenolol or propranolol, nor was there significant change in pulmonary pressure, vascular resistance, or cardiac output. Thus oxprenolol closely parallels the effects of propranolol in essential hypertension. The negative chronotropic action of both drugs is more marked than their antihypertensive activity.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Heart Rate; Hemodynamics; Humans; Hypertension; Middle Aged; Myocardial Contraction; Oxprenolol; Posture; Propranolol; Renin; Stress, Physiological; Time Factors
Antiarrhythmic effect of oxprenolol on halothane-epinephrine and coronary ligation induced ventricular arrhythmias in beagle dogs.Japanese Journal of Pharmacology Aug 1978Antiarrhythmic effects of oxprenolol, a beta-blocker, were studied quantitatively on arhythmias produced by epinephrine during halothane anesthesia and by two-stage...
Antiarrhythmic effects of oxprenolol, a beta-blocker, were studied quantitatively on arhythmias produced by epinephrine during halothane anesthesia and by two-stage coronary ligation, and were compared to those of other beta-blockers, propranolol and Kö 1400, which have been already reported. Though oxprenolol has potent beta-blocking activity, the antiarrhythmic effect on halothane-epinephrine arrhythmia was significantly weaker than those of propranolol and Kö 1400. The effective dose of oxprenolol was 60 +/- 18 microgram/kg (mean +/- S.E., N = 6), which is in the range of the so-called beta-adrenergic blocking dose. The weaker antiarrhythmic effect of oxprenolol as compared to propranolol and Kö 1400 is probably due to the intrinsic positive chronotropic effect, which is most clearly observed in oxprenolol as compared to the other two drugs. As for two-stage coronary ligation arrhythmia, oxprenolol suppressed only that observed 48 hours after coronary ligation using higher doses (5 to 10 mg/kg). Other beta-blockers also showed similar effects. Because of the high doses necessary for the antiarrhythmic effects on the coronary ligation arrhythmia, the mechanism for suppressing the arrhythmia is probably due to the local anesthetic action of the beta-blockers.
Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Dogs; Epinephrine; Female; Halothane; Heart Ventricles; Ligation; Male; Oxprenolol