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
Comparison of pharmacokinetic profiles of single and multiple doses of a slow release Oros oxprenolol delivery system in young normotensive and elderly hypertensive...British Journal of Clinical Pharmacology Apr 1986Oxprenolol in an Oros 8/130 sustained release osmotic pump system (equivalent to 120 mg oxprenolol hydrochloride in a conventional formulation and releasing 8 mg h-1)... (Comparative Study)
Comparison of pharmacokinetic profiles of single and multiple doses of a slow release Oros oxprenolol delivery system in young normotensive and elderly hypertensive subjects.
Oxprenolol in an Oros 8/130 sustained release osmotic pump system (equivalent to 120 mg oxprenolol hydrochloride in a conventional formulation and releasing 8 mg h-1) was given to eight normal young subjects (mean age 23 years) and eight elderly hypertensive patients (mean age 77 years). The plasma concentration-time profiles of oxprenolol were determined over 32 h using gas liquid chromatography after the initial dose and following seven doses. The elderly patients had a significantly higher AUC and maximum plasma oxprenolol concentration following both the first and final doses studied. It is unlikely that this difference is due to a prolonged absorption phase in the elderly patients. Reduced drug clearance seems the most probable explanation.
Topics: Adult; Age Factors; Aged; Blood Proteins; Delayed-Action Preparations; Drug Evaluation; Female; Humans; Hypertension; Kinetics; Liver; Male; Oxprenolol; Protein Binding
Journal of the American College of... Nov 1985In 736 patients, 24 hour electrocardiographic recordings were performed 14 to 36 days after acute myocardial infarction before the start of randomized treatment with 320... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
In 736 patients, 24 hour electrocardiographic recordings were performed 14 to 36 days after acute myocardial infarction before the start of randomized treatment with 320 mg of slow release oxprenolol (n = 358) or placebo (n = 378). Follow-up 24 hour electrocardiographic recordings were obtained 5 to 12 days (median 10) and 3, 6 and 12 months after the first administration of the study medication. Oxprenolol-treated patients had a significantly lower daytime heart rate as compared with the placebo group, whereas no difference was found at night. At baseline, 22.1% of the patients allocated to oxprenolol treatment and 29.6% of the placebo group had more than 30 ventricular extrasystoles in 1 hour at least once during 24 hour monitoring; multiform ventricular extrasystoles were present in 58.4 and 62.7%, ventricular couplets in 29.6 and 33.9% and ventricular tachycardia (3 or more consecutive ventricular extrasystoles) in 21.5 and 20.9% of the oxprenolol-treated and placebo-treated patients, respectively. During the 1 year follow-up period, the prevalence of these arrhythmias did not change significantly in either treatment group. There was a trend toward a reduction in the daytime frequency of ventricular couplets in the oxprenolol group. After 3 and 6 months, only multiform ventricular extrasystoles were significantly less frequent in the oxprenolol group than in the placebo group (47.4 and 42.7% versus 59.7 and 57.9%, respectively). Twelve months after the acute event, however, multiform ventricular extrasystole frequency was the same in both groups of patients (52.1 versus 51.0%, respectively). Thus, oxprenolol had a weak suppressant effect on ventricular tachyarrhythmias in survivors of myocardial infarction.
Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Myocardial Infarction; Oxprenolol; Prospective Studies; Random Allocation
British Journal of Clinical Pharmacology Oct 1985Single doses of bucindolol 50, 100 and 200 mg were compared to placebo and single doses of oxprenolol 40, 80 and 160 mg in seven patients with mild hypertension, in a... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Single doses of bucindolol 50, 100 and 200 mg were compared to placebo and single doses of oxprenolol 40, 80 and 160 mg in seven patients with mild hypertension, in a double-blind randomized study. Both bucindolol and oxprenolol inhibited exercise induced tachycardia. The mean maximum inhibition of exercise heart rate was similar after each dose of both drugs (20%, P less than 0.001). Bucindolol produced a significantly greater reduction in blood pressure than either oxprenolol or placebo. This was most apparent in standing systolic and diastolic and post-exercise systolic blood pressures between 1 and 2 h after dosing and was dose-related. All seven patients experienced adverse effects related to hypotension within the first 2 h after ingestion of bucindolol 200 mg. Plasma concentrations of oxprenolol, bucindolol or 5-hydroxy-bucindolol, sampled 2 h after dosing, could not be related to either the changes in blood pressure or to the occurrence of symptoms. The results emphasise the need for careful dose-finding of new drugs prior to their more widespread evaluation in phase 3 studies.
Topics: Adrenergic beta-Antagonists; Adult; Blood Pressure; Exercise Test; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxprenolol; Posture; Propanolamines; Time Factors
Exercise and resting blood pressure and heart rate changes 24 h after dosing in patients with essential hypertension receiving 16/260 oxprenolol Oros once daily.British Journal of Clinical Pharmacology 1985Nineteen patients receiving oxprenolol slow-release (SR) 160 mg (three patients) or 320 mg (16 patients) once daily for mild to moderate hypertension were treated with...
Nineteen patients receiving oxprenolol slow-release (SR) 160 mg (three patients) or 320 mg (16 patients) once daily for mild to moderate hypertension were treated with oxprenolol Oros 16/260 once daily for 3 weeks following a 2 week placebo wash-out period. Repeated dosing with both Oros and SR oxprenolol preparations, in comparison with placebo, significantly reduced supine systolic and diastolic blood pressures, and pulse rate at 24 h after dosing. Single Oros doses also significantly reduced pulse rate and diastolic, but not systolic, blood pressure at 24 h. The reduction in supine systolic blood pressure was greater during repeated dosing with oxprenolol SR than after a single dose of the Oros preparation. Control of supine diastolic blood pressure (less than or equal to 90 mm Hg) at 24 h after dosing was achieved in 13 out of 18 patients with oxprenolol SR (two out of three patients given 160 mg, and 11 out of 15 given 320 mg). Similar control was achieved in 11 out of 18 patients after a single dose of oxprenolol Oros, and in 13 out of 17 patients treated for 3 weeks. The mean percentage reduction in exercise heart rate (EHR) compared to placebo, at 24 h after dosing, was 16% following Oros treatment for 3 weeks, and 12% following SR administration. After a single dose of oxprenolol Oros EHR, was reduced by 9% at 24 h compared to placebo. At 3 weeks the Oros formulation was significantly better than the SR tablet at reducing EHR. Oxprenolol Oros 16/260 was effective over 24 h and well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Blood Pressure; Delayed-Action Preparations; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxprenolol; Physical Exertion
A multiple dose comparative study of the pharmacodynamic and pharmacokinetic behaviour of polymer-matrix and Oros dosage forms of oxprenolol in healthy volunteers.British Journal of Clinical Pharmacology 1985A new osmotic drug delivery system (Oros) has been evaluated in multiple-dose studies in young healthy volunteers as a sustained-release vehicle for once-daily... (Clinical Trial)
Clinical Trial Comparative Study
A new osmotic drug delivery system (Oros) has been evaluated in multiple-dose studies in young healthy volunteers as a sustained-release vehicle for once-daily administration of oxprenolol. Two Oros systems were examined in two separate studies, one containing 170 mg oxprenolol succinate with an initial zero-order release rate of 10 mg/h, and the other containing 260 mg oxprenolol succinate with an initial release rate of 16 mg/h. These were compared respectively with conventional oxprenolol hydrochloride (Trasicor) 80 mg twice daily and polymer-matrix oxprenolol hydrochloride (Slow Trasicor) 160 mg once daily. Variations in mean plasma levels and beta-adrenoceptor blockade (measured by inhibition of exercise tachycardia) were considerably reduced on the 10/170 Oros once-daily compared with the Trasicor 80 mg twice-daily regimen. With both formulations there was no significant change in mean plasma concentrations or areas under the curve after 8 days' treatment, and similar pre-dose plasma concentrations were obtained. There was significant inhibition of exercise tachycardia throughout 24 h after the 10/170 Oros on the eighth day. The 16/260 Oros system gave smoother pharmacokinetic and pharmacodynamic profiles, and on repeated dosing a higher mean pre-dose plasma oxprenolol concentration than Slow Trasicor. Drug availability was similar for the two dose forms, suggesting an acceptable level of absorption of oxprenolol from most of the gastrointestinal tract. On the eighth day exercise heart rate was significantly reduced throughout 24 h with 16/260 oxprenolol Oros, but only between 1 and 15 h with Slow Trasicor.
Topics: Adult; Blood Pressure; Delayed-Action Preparations; Double-Blind Method; Female; Heart Rate; Humans; Kinetics; Male; Oxprenolol; Physical Exertion; Pulse
British Journal of Clinical Pharmacology Sep 1984Thirty-two pregnant hypertensive patients were treated with oxprenolol administered in combination with dihydralazine as Trasipressol tablets. Before delivery,...
Thirty-two pregnant hypertensive patients were treated with oxprenolol administered in combination with dihydralazine as Trasipressol tablets. Before delivery, oxprenolol was demonstrable in the maternal plasma and the amniotic fluid. The free fraction of oxprenolol in the maternal serum (15% +/- 7.8; mean +/- s.d.; n = 25) was similar to that in normal serum. At the end of delivery, oxprenolol was found in both the maternal and umbilical plasma in most cases. Measurable, but low oxprenolol concentrations were present in the newborn plasma. After delivery, oxprenolol was demonstrable in the maternal plasma and breast milk. An infant weighing 3 kg and consuming 500 ml of breast milk per day would receive a maximum dose 60 times less than the normal daily dose for a hypertensive adult (4 mg/kg).
Topics: Adolescent; Adult; Female; Humans; Hypertension; Infant, Newborn; Maternal-Fetal Exchange; Milk, Human; Oxprenolol; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular; Time Factors