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PubMed1981

Metoprolol and propranolol in the treatment of essential hypertension - a long-term comparative study.

After a two-week run-in period on placebo, fifty-two patients with benign essential hypertension (WHO classes I or II) were treated with individually titrated doses of metoprolol or propranolol for 36 weeks. If blood pressure was not satisfactorily controlled by beta-blockers, a saluretic diuretic and, if necessary, hydralazine were added. Five patients on metoprolol and four on propranolol received such additional therapy. Fifty patients completed the trial. The final mean daily doses of metoprolol and propranolol were 327 mg and 282 mg, respectively. As the beta1-adrenoceptor-blocker potency of the drugs is 4:5 (i.e. 50 mg metoprolol corresponds to 40 mg propranolol in reducing exercise-induced tachycardia) the relative dose of metoprolol seemed to be slightly lower than that of propranolol. Compared to the values during the placebo period, heart rate, systolic and diastolic blood pressure in both the supine and standing position were significantly reduced in both groups after 12, 24 and 36 weeks' treatment with active drug. At the end of the treatment period, the mean reductions in supine blood pressure were 26/15 and 16/9 mm Hg in the metoprolol and propranolol groups, respectively. The reductions in supine diastolic and standing systolic blood pressures were significantly greater in the metoprolol than the propranolol group at this time.

Adult↗
PubMed1981

The relative roles of sodium and renin in the hypertension of renal disease. An assessment based on the response to frusemide and propranolol.

Twenty-seven patients with hypertension and varying degrees of renal failure were studied before and during the administration of frusemide. In 15 patients studies were repeated following the addition of propranolol. Mean exchangeable sodium was increased before the introduction of frusemide or propranolol in patients with azotemia, possibly due in part to the administration of other antihypertensive drugs, and was reduced to normal during frusemide treatment increasing slightly but significantly following the addition of propranolol. Blood pressure fell significantly with frusemide but there was no further significant fall with propranolol. The relationship of change in blood pressure to change in exchangeable sodium with frusemide did not reach significance. There was no relationship between changes in blood pressure and changes in plasma renin activity with frusemide, suggesting that the blood pressure response to frusemide is not limited by the rise in renin. The fall in blood pressure following the addition of propranolol was proportional to the dose of the drug but inversely proportional to the change in renin suggesting that renin levels are to some extent determined by the blood pressure response to propranolol rather than themselves determining that response. Serum creatinine was significantly increased during treatment with frusemide probably due to a combination of the effects of sodium depletion and the natural progression of the underlying renal disease rather than to nephrotoxicity. The further slight increase in serum creatinine following the addition of propranolol is in keeping with the reported effect of this drug on renal blood flow and glomerular filtration rate in patients without renal disease.

Adolescent↗
PubMed1982

Continuous propranolol infusion following abdominal surgery.

Thirteen patients given long-term propranolol hydrochloride therapy for heart disease required 15 abdominal surgical procedures. On each occasion, propranolol therapy was maintained postoperatively by continuous intravenous infusion. Duration of infusion ranged from one to nine days, and each infusion was monitored with frequent measurements of serum propranolol concentrations. In patients with normal hepatic and renal function, therapeutic serum propranolol levels were attained with a narrow dose range averaging 3.0 mg/hr, irrespective of body weight. All patients had postoperative courses free of complications attributable to beta-blockade. This form of therapy appears to protect against sympathetic stimulation during the perioperative period and to prevent the propranolol withdrawal syndrome in such patients. Continuous propranolol infusion might also be useful in other clinical situations, such as acute aortic dissection or severe thyrotoxicosis, where predictable therapeutic serum propranolol levels could be maintained when oral therapy was contraindicated.

Abdomen↗
PubMed1982

Phospholipid metabolism changes in rat tissues in vitro after injections of propranolol.

When added to incubations in vitro. (+/-)-propranolol, a cationic amphiphilic drug, causes profound alterations in incorporation of [32P] orthosphosphate into rat cerebral cortex phospholipids. These include increases in the labeling of phosphatidic acid and polyphosphoinositides abd a decrease in the labeling of phosphatidylcholine. Similar changes occurred in a dose-dependent manner in incubations of cerebral cortex mince, prepared from animals injected i.p. 30 min before death with doses of propranolol ranging from 7.5 to 45 mg/kg. All changes in total incorporation and in labeling pattern had disappeared 3 hr after injection, indicating the reversibility of the effect. Repeated injections of low doses of propranolol (7.5 mg/kg) brought about significant changes in the labeling of brain cortex mince phospholipids, and especially a reduction in total incorporation. Addition of propranolol to kidney and liver minces caused reductions in the labeling of phosphatidylcholine and phosphatidylethanolamine and selective increases in the labeling of acidic lipids, restricted to phosphatidic acid in liver and phosphatidylinositol in kidney. After injection of 45 mg of propranolol per kg, but not at 15 mg/kg, some alterations in the labeling pattern were observed in liver and kidney minces. The differential response of tissues to propranolol injections can be explained on the basis of the pharmacokinetics of drug distribution and clearance and metabolic capacities of the tissues. Changes in phospholipid metabolism may be in part responsible for deleterious side effects that can occur during therapy with high doses of propranolol.

Animals↗
PubMed1982

[Effect of propranolol on lipid metabolism in rats].

The effects of propranolol on lipid metabolism were studied in rats. Male Sprague Dawley rats at 5 weeks of age were used. Rats were given 5-10 mg/kg/day of propranolol subcutaneously or 10 mg/kg/day orally for 8 weeks. Serum non-esterified fatty acids and triglyceride were lowered in the oral treatment with propranolol but not changed in the subcutaneous one. Total serum cholesterol tended to decrease at the early weeks of treatment and increased at later weeks of treatment as compared with the control group. alpha-Lipoprotein was higher and beta-lipoprotein was lower in propranolol-treated groups than that in the control group. Serum lecithin cholesterol acyl transferase activity and high density lipoprotein were higher in propranolol-treated groups at 1st and 8th week of treatment. Total cholesterol in the liver decreased at the 8th week of treatment, but triglyceride in the liver did not change. These results suggest that propranolol inhibits the hormone sensitive lipase activity through adenyl cyclase at the early weeks of treatment, but this effect is reduced by homeostasis at the later weeks of treatment. There were some differences in serum lipids and enzyme activities between the oral and subcutaneous treatments. This would be related to the first pass effect of propranolol.

Administration, Oral↗
PubMed1981

[Treatment of acute myocardial infarction with betareceptor blocking agents. I. Hemodynamic effects of Propranolol in combination with digitalis (author's transl)].

In the acute stage of transmural myocardial infarction, 22 patients ranging in age from 34 to 76 (mean 61.6) were given propranolol- because of its alleged myocardium-protecting properties - intravenously at a dosage of 0.03 to 0.1 mg/kg body weight under conditions of continuous hemodynamic control. Subsequently, the influence of digoxin, administered i. v. at a dosage of 0.01 my/kg body weight, on the negative-inotropic propranolol effects was examined. A hemodynamic comparison was made of the effects of propranolol before and after digitalis administration. In patients with compensated cardiac function (group 1, 16 patients), the propranolol-induced drop in the left ventricular stroke-work-index and rise in the left-ventricular filling pressure was completely compensated again by digitalis. The frequency-decreasing propranolol effect was nor influenced by digitalis. In patients with cardiac decompensation (group 2, 6 patients) digitalis only led to a renewed compensation of the left-ventricular stroke-work-index, the rise of the left-ventricular filling pressure remained unaffected. It follows from that, in cases of myocardial infarction without cardial decompensation, propranolol requires concomitant digitalisation. In cases of already existent myocardial insufficiency, propranolol can produce an unfavorable increase of the decompensation signs.

Acute Disease↗
PubMed1978

Effect of high dose d-l propranolol on the renin-angiotensin system in glycerol induced acute renal failure in rat.

Stimulation of the renin-angiotensin system has been implicated in the pathogenesis of post-ischemic and nephrotoxic acute renal failure. This study was designed to determine the effect of d-l propranolol in glycerol induced acute renal failure in rats. 50% glycerol administered alone, induced a significant rise in blood urea and plasma renin concentration but no significant change in renal renin concentration. When administered with d-l propranolol (10 mg/kg body weight in 5 subcutaneous injections), mean blood urea, plasma renin and renal renin concentrations were not significantly different from the preceding group. Propranolol alone, administered in the same fashion, unexpectedly induced a rise in plasma renin concentration (p less than 0.05) while blood urea and renal renin concentrations were unchanged. Considering the unusually high dose of propranolol used, a second protocol was devised to compare the effects of d-l propranolol, in doses of 10 mg/kg and 1 mg/kg. Plasma renin concentration rose after high dose propranolol, but decreased, although not significantly, after administration of 1 mg/kg. Renal renin concentration was unchanged. High dose d-l propranolol, does not protect rats against glycerol induced acute renal failure. Contrarily to the usual 1 mg/kg dose, it was found surprisingly to increase renin release.

Acute Kidney Injury↗
PubMed1995

Trimetazidine European Multicenter Study versus propranolol in stable angina pectoris: contribution of Holter electrocardiographic ambulatory monitoring.

The major objective of the Trimetazidine European Multicenter Study (TEMS) was to compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg 3 times daily) with those of propranolol (40 mg 3 times daily). The inclusion criteria were based on an abnormal response to a multistage exercise test. After 3 months of treatment the improvements noted in all exercise testing data were similar in the trimetazidine and propranolol groups; similar data were obtained for the grades and severity of anginal attacks during daily life (from patient diaries). A 24-hour Holter monitoring was performed at entry and at the end of the study, but an abnormal Holter monitoring (1-mm ST-segment depression during at least 1 minute) was not an inclusion criterion. This explains why at entry only 50% of the patients in both groups had an abnormal Holter recording. After 3 months of treatment, there were no significant differences between the 2 groups, but we observed a trend toward a decrease in ambulatory ischemia in the trimetazidine group and a trend toward an increase in ambulatory ischemia in the propranolol group. These data in the propranolol group are in total disagreement with the available literature on beta blockers, which was due to a totally erratic behavior pattern in 2 patients in the propranolol group. When we excluded these 2 erratic cases from the propranolol group and extended our analysis to all available paired comparisons (day -14 to day 30 and day 0 to day 90), we were able to compare 44 and 60 observations, both off therapy and on either propranolol or trimetazidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMedDate not supplied

Cyclandelate versus propranolol in the prophylaxis of migraine--a double-blind placebo-controlled study.

The aim of the present study was to ascertain the comparative efficacy of cyclandelate, a migraine prophylactic with calcium overload blocking properties, versus propranolol, a non-selective beta-adrenergic blocker, and placebo. Based on different statistical analysis procedures (including time series analysis) a responder and nonresponder evaluation for cyclandelate and propranolol was performed. In addition, an attempt was made to identify the dose relationship of the various drugs on headache parameters. In a double-blind placebo-controlled study 84 patients were treated in a placebo run-in phase (4 weeks). The patients were then randomized by the statistical criterion of placebo responder and nonresponder to either the cyclandelate or the propranolol group. The total treatment period included a low-dosage phase (8 weeks) and high-dosage phase (8 weeks). All patients kept a headache diary before, during and after treatment. The data were assessed by time series analysis (ARIMA), as well as by analysis of variance and nonparametric statistics. Based on ARIMA statistics, 39.3% of the patients showed a significant improvement of migraine during treatment with cyclandelate compared with 29.4% placed on propranolol. Higher doses of cyclandelate and propranolol were more effective. Using the qualitative response-criterion of a 50% reduction in migraine symptoms, cyclandelate showed a response in 67.9% and propranolol in 41.2% of all cases. It can therefore be concluded that cyclandelate as well as propranolol are two comparable substances in the prophylactic treatment of migraine, with cyclandelate showing fewer side effects.

Adolescent↗
PubMed1976

Pharmacokinetics of propranolol: a review.

The pharmacokinetics of propranolol vary according to the route and duration of administration. After i.v. administration, the decline in drug concentrations is biphasic and the drug is cleared very efficiently by the liver, so that its elimination is dependent largely on liver blood flow. Although the drug is some 90-95% bound to plasma, hepatic removal is so avid that both bound and free forms are extracted. Consequently, hepatic elimination is unaffected by drug binding in blood, In contrast, the distribution of drug into the tissues is reduced by plasma binding, so that drug half-life (T 1/2), which varies from 11/2-3 hours among individuals is more prolonged in people with relatively low plasma binding. Recent evidence shows that at all times after i.v. administration the beta-blocking effects of propranolol are related to its plasma concentrations according to the receptor theory. In addition individual differences in the response due to a given total concentration are largely due to variations in plasma binding, the drug's effects being a function of free (unbound) drug in plasma water. After the administration of single oral doses, hepatic extraction remains high and much of the dose is eliminated from hepatic portal blood during transfer from the gut, so that little drug reaches the systemic circulation. In addition, significant amounts of an active metabolite, 4-OH propranolol, are produced so that 2 hours after dosing, propranolol appears more potent that its plasma levels would suggest. With continued administration, the avid removal process becomes saturated, extraction ratio falls and propranolol accumulates some 2-fold. Drug T 1/2 is prolonged to 3-6 hours under these conditions, the ratio of propranolol to its active metabolite increases so that most of its effects can be attributed to the parent drug. Perhaps the most important kinetic fact to emerge is the 20-fold variation in plasma levels found after chronic administration of the same oral dose to different patients. This accounts for most of the individual variation in dosage requirements. Concerning propranolol withdrawal, there is no evidence that the effects of the drug last longer than appropriate for its T 1/2, so that larger doses last longer. Nonetheless, 24-48 hours is more that sufficient for the effects of the drug to dissipate. In view of the rebound angina, arrhythmias and infarction that may occur, abrupt withdrawal should be avoided if possible.

Biological Availability↗
PubMed1976

Propranolol in the treatment of angina: a review.

The use of beta-adrenergic blocking drugs in angina pectoris was one of the original indications for these drugs suggested by Black. An anti-anginal effect was demonstrated with the first beta-adrenergic blocking drug, pronethalol, that was used clinically. This benefit in angina was confirmed in the early trials with propranolol in 1964-65. Although some definite anti-anginal effect can be demonstrated with low fixed dosage, evidence suggested that those trials which used a higher and a variable dose displayed a greater anti-anginal action of the drug. After a two dose trial (Gillam and Prichard, 1966,) demonstrated a dose dependent anti-anginal effect, a log-dose response study demonstrated a progressive reduction in angina attacks as dosage was increased (Prichard and Gillam, 1971). While a highly significant effect was found with an average dose of 52 mg a day a progressive reduction in angina attacks was found with logarithmic increases in dosage up to an average of 417 mg a day. Dosage in this trial was adjusted to produce a supine heart rate of 55-60 beats/minute provided this was not prevented by side effects. As the dosage of 417 mg a day was still on the straight line part of the dose response curve and therefore suboptimal, we not adjust dosage to produce a standing heart rate of 55-60. Fully meaningful comparative trials require that optimum dose of the drugs being compared are used. A variable dose comparative trial comparing propranolol and practolol, showed propranolol was the more effective agent. More recently a variable dose comparative trial of sotalol and propranolol indicated propranolol had greater anti-anginal action although sotalol, unlike practolol, was more effective than low dose propranolol. The use of beta-blocking agents in angina pectoris is relatively safe provided that the contraindications of asthma and cardiac insufficiency are observed and that treatment is commenced at a low dosage. The most dramatic change in the sympathetic environment of the heart takes place when treatment with a beta-blocking drug is commenced. The greatest danger of precipitating heart failure is therefore at the beginning of treatment even with a small starting dose. Once treatment has begun even an increase of 25% per dose represents a small pharmacological increment as there is no great change in the sympathetic drive to the heart. The larger dosage of beta-blocking drugs required for optimum treatment of angina may be gradually approached, but it has been my experience that heart failure is not likely to be precipitated at larger doses, provided they are not used initially. In other than mild angina pectoris the average optimum dosage of propranolol is 500-800 mg a day, similar, or perhaps more than the average dose in hypertension.

Alprenolol↗
PubMedDate not supplied

Metabolic kinetics of pseudoracemic propranolol in human liver microsomes. Enantioselectivity and quinidine inhibition.

The enantioselective formation kinetics of 4-hydroxypropranolol (4-HOP), 5-hydroxypropranolol (5-HOP), and desisopropylpropranolol (DIP) were characterized over a wide substrate concentration range (1-1000 microM) in human liver microsomes using deuterium-labeled pseudoracemic propranolol. Existing data suggest that several microsomal cytochrome P-450 enzymes are involved in the oxidative metabolism of propranolol in humans. Biphasic kinetics were observed in the formation of all three metabolites, indicating the involvement of at least two enzymes in each pathway. The R/S ratios for the formation of all three metabolites varied with respect to the substrate concentration, lending further support to the contribution of two or more enzymes with differing KM's and enantioselectivity. The high-affinity 4-hydroxylation process showed a strong R-enantioselectivity. The low-affinity component of 4-hydroxylation also exhibited a preference for R-(+)-propranolol, although to a lesser degree than the high-affinity component. A similar pattern of enantioselectivity was observed for 5-hydroxylation, except that R/S ratio showed an initial increase followed by a decrease as the propranolol concentration increased beyond 200 microM. Formation of DIP was R-enantioselective at low substrate concentrations, whereas an opposite enantioselectivity was observed at high propranolol concentrations. The metabolism of propranolol in the presence of nanomolar concentrations of quinidine (a selective inhibitor of P-450 2D6) was studied at concentrations of pseudoracemic propranolol in the high- and low-affinity regions. A significant inhibition of 4- and 5-hydroxylation was observed, whereas N-dealkylation was not affected by quinidine. The inhibition of 4-hydroxylation was slightly enantioselective toward R-enantiomer. Quinidine had no significant effect on the low-affinity component for 4-hydroxylation. Although the inhibition of 4- and 5-hydroxylation at the high-affinity site was extensive, complete inhibition was not achieved even at the highest quinidine concentration (10 microM). Data could be fitted to a mixed-type inhibition kinetics resulting from multiple high-affinity hydroxylases. Our in vitro results indicate that formation of 4-HOP and 5-HOP is mediated by more than one P-450 enzyme with major contribution from P-450 2D6, whereas the formation of DIP is catalyzed by two or more P-450 enzymes other than 2D6.

Biotransformation↗
PubMed1994

[Levels of free fatty acids in plasma, K coefficient and insulin secretion stimulated by intravenous glucose load in patients with hyperthyroidism taking propranolol or acebutolol].

UNLABELLED: The aim of this study was to determine the relationships between plasma free fatty acids levels (FFA) and impaired glucose tolerance in hyperthyroid patients in basal condition and after propranolol and acebutolol treatment, i.e. after lipolytic blockade leading to a decrease in plasma FFA levels. 31 untreated hyperthyroid patients and 12 normal subjects of matched control group were studied. In all IVGTT was performed. 19 patients with normal K values were randomized to treated with either propranolol 160 mg daily (10 persons) or acebutolol 400 mg daily (9 persons). 12 patients with low K values were randomized to treated with either propranolol (5 persons) or acebutolol (7 persons). After 7 days on treatment a second IVGTT was carried. In all blood samples were glucose, FFA and insulin levels determined, in samples taken at 0 T3 and T4 too. T3, T4 and insulin were measured by the radioimmunoassay, glucose by the glucose oxidase method, FFA by the colorimetric method. In hyperthyroid patients with low K value significantly higher plasma concentrations of FFA were found compared to control and after propranolol or acebutolol treatment no differences in FFA levels between hyperthyroid patients and control were observed. In patients with low K value acebutolol but not propranolol normalized K value and propranolol but not acebutolol significantly decreased acute phase of insulin secretion. In patients with normal K value plasma glucose and insulin concentrations as well K value were not altered during propranolol or acebutolol treatment. CONCLUSIONS: 1. Hyperthyroid patients with low K value differ from healthy subjects higher plasma FFA levels, 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acebutolol↗
PubMed1993

Bronchial responsiveness to inhaled propranolol in asthmatic children and adults.

Inhaled propranolol (P) was administered to a population which included asthmatic children (30 subjects) and adults (43 subjects): 1) to investigate the determinants of induced bronchial response; 2) to examine the relationship with treatment requirements; 3) to determine the relationship with responsiveness to methacholine (M) and ultrasonically nebulized distilled water (UNDW) (50 subjects); and 4) to establish the short-term repeatability of bronchial response to propranolol compared with methacholine (22 subjects). Bronchial response to propranolol and methacholine was expressed as the cumulative provocative dose (PD20 in mumol) and responsiveness to UNDW as the provocative output (PO20 in ml.min-1) producing a 20% fall in forced expiratory volume in one second (FEV1). Response to propranolol was significantly related to the degree of responsiveness to methacholine, but not to age, gender, presence of atopy, age at asthma onset, or baseline FEV1. PD20P was measurable in all but three subjects. A significant difference in mean PD20M but not in PD20P was found between subjects requiring more anti-asthmatic treatments compared to those without therapy. The difference between geometric mean PD20P and geometric mean PD20M was 14.1. PO20UNDW was measurable in only 21 out of 50 subjects. Both PD20P and PD20M were significantly lower in responders to UNDW than in nonresponders. Reproducibility of PD20P was comparable to that of PD20M (coefficients of repeatability: 1.17 and 1.09). We conclude that bronchial responsiveness to propranolol is safely measurable in most children and adults with asthma. Repeatability of bronchial response to propranolol is comparable to that of methacholine. Moreover, responsiveness to propranolol is not a predictor of treatment requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Influence of aging on the oxidative and conjugative metabolism of propranolol.

The influence of aging on the hepatic metabolism of propranolol, i.e. conjugation, side-chain oxidation and ring oxidation, was investigated in 32 in-patients aged 30 to 84 yrs. Plasma propranolol concentration and main urinary metabolites [propranolol glucuronide (PPLG), naphthoxylactic acid (NLA), and 4-hydroxypropranolol (40HP)] were determined after a single oral dose of 20 mg propranolol. There were significant correlations between age and 1) maximum propranolol concentration, 2) area under the plasma concentration-time curve, and 3) elimination half-life. The apparent oral clearance of propranolol was inversely correlated with age. Partial metabolic clearance (PMC) to 40HP (ring oxidation) and PMC to NLA (side-chain oxidation) were significantly correlated with age, while PMC to PPLG was not. These observations suggest that there are age-related reductions in two oxidizing capacities, while there is no significant influence of aging on the conjugating capacity. The age-related reduction in oral clearance of propranolol may be mainly caused by the decline in the capacity of two different oxidation pathways.

Adrenergic beta-Antagonists↗
PubMed1996

Propranolol stereoselectively inhibits alpha-adrenoceptor-mediated vasoconstriction in mesenteric arterial beds of rats.

1. The optical isomers of propranolol were compared for their effects on pressor responses to adrenergic and non-adrenergic vasoconstrictors in mesenteric arterial beds of rats. 2. R(+)-propranolol (10(-7)-10(-5) M) had no effect on vessel preparations stimulated with noradrenaline, methoxamine, or arginine-vasopressin. 3. S(-)-propranolol 10(-7) M did not alter pressor responses to noradrenaline. However, S(-)-propranolol 10(-6) and 10(-5) M inhibited vasoconstriction induced by noradrenaline. This effect was similar in the presence of indomethacin 3 x 10(-6) M. 4. S(-)-propranolol 10(-5) M also inhibited vasoconstriction induced by methoxamine, shifting the dose-response curves to the right, but did not affect pressor responses to arginine-vasopressin. 5. Schild analysis for equilibrium vasoconstrictor responses to methoxamine indicated stereoselective competitive alpha-adrenoceptor antagonism by propranolol. 6. These data suggest selective inhibition of alpha-adrenoceptor-mediated vasoconstriction by S(-)-propranolol at higher concentrations by competitive alpha-adrenoceptor antagonism.

Adrenergic alpha-Agonists↗
PubMed2006

Use of fluorescence shift and fluorescence anisotropy to evaluate the re-binding of template to (S)-propranolol imprinted polymers.

The binding of (R)- and (S)-propranolol to an (S)-propranolol imprinted polymer in organic and aqueous solutions has been studied using fluorescence. The amount of propranolol that binds can be measured by separating non-bound propranolol from the polymer by centrifugation, and measuring the fluorescence intensity. However, this work demonstrates that other measurements can indicate how much propranolol has bound without the need to separate bound and non-bound analyte. In toluene + 0.5% AcOH, and in aqueous buffer (25 mM citrate pH 6 + 0.5% Triton X100) the fluorescence anisotropy increases as the fraction of analyte bound to the polymer increases. In aqueous buffer, binding to the polymer is also accompanied by a change in the relative intensities of fluorescence at 322 nm and at 352 nm. These non-separation techniques have been used to show that the imprinted polymer binds more (S)-propranolol than a non-imprinted polymer, and at least in organic solvent, shows selectivity for (S)- over (R)-propranolol.

Journal Article↗
PubMed1999

Differential permeation of propranolol enantiomers across human skin in vitro from formulations containing an enantioselective excipient.

This work tested the hypothesis that a stereospecific topical formulation could be used to engineer differential permeation rates for each enantiomer of an applied racemate across human skin in vitro. Racemic and enantiomerically pure R or S propranolol HCI were formulated with cellulose tris(3,5-dimethyl phenyl carbamate) (CDMPC) and applied to excised human skin using side-by-side Franz-type diffusion cells. When the pure enantiomers were used, there was a marked difference between the penetration rates of R and S propranolol (flux ratio: 2.06; P = 0.04). When racemic propranolol was used, the difference was reduced, although still statistically significant (flux ratio: 1.2; P = 0.08), particularly in view of the differential activities of the two enantiomers. Control experiments, in which no CDMPC was present, produced equal permeation rates. The results can be rationalised in terms of differential adsorption onto CDMPC within the vehicle, whereby S-propranolol is preferentially bound relative to R-propranolol. This causes an imbalance in the apparent donor phase concentrations that (in accordance with Fickian diffusion laws and thermodynamic activity) gives rise to differences in permeation rates. The diminished differential observed when the racemate was used, rather than individual enantiomers, is less easily rationalised. In this work, it was the permeation of the eutomer (S-propranolol) that was retarded, although the general principle of stereoselectively retarded skin permeation has been established.

Chromatography, High Pressure Liquid↗