Plasma Propranolol Levels Research Articles

Combination propranolol and bepridil therapy in stable angina pectoris

The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p < 0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 ± 1.2 minutes from a baseline of 7.3 ± 2.2 with bepridil plus propranolol compared with an increase of 0.02 ± 1.3 minutes from a baseline of 7.6 ± 2.9 with placebo plus propranolol (p < 0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p < 0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p < 0.06) and total work (p < 0.03) compared with placebo plus propranolol therapy. Resting heart rate was reduced a maximum of 2 beats/min with combination treatment compared with propranolol alone, and no differences in blood pressure between treatment groups were observed. There were no clinically significant rhythm changes on Holter ECG with combination treatment, and bepridil treatment had no effect on plasma propranolol levels. Bepridil did prolong the QTc interval on resting ECG by a mean of 37 ± 39 millisecond. Adverse effects were mild with bepridil plus propranolol and greater in frequency than those with placebo plus propranolol. With cessation of bepridil, patients returned toward the angina frequency and exercise tolerance levels seen at baseline with propranolol alone. The addition of bepridil to propranolol provided safe and effective antianginal therapy in patients whose angina was not controlled by propranolol alone.

Comparison of kinetic interactions of nadolol and propranolol with cimetidine

Plasma levels of nadolol and propranolol following a single 80 mg dose of each beta blocker in the presence and absence of cimetidine were determined in 12 healthy male subjects. Cimetidine increased ( p < 0.01) the area under the plasma concentration-time curve and peak plasma levels of propranolol by 46% and 35%, respectively. Nadolol kinetics were not altered significantly by cimetidine, except for a reduction in time to reach peak concentrations. The higher blood levels of propranolol during administration of cimetidine were not associated with any changes in resting blood pressure or heart rate compared with propranolol alone. Cimetidine had no effect on elimination half-lifes or apparent mean residence times for either beta blocker.

Antihypertensive effect and degree of beta-adrenoceptor blockade after short-term and semi-chronic propranolol therapy.

In patients with normal-renin, mild (n = 6) or moderate (n = 6) hypertension, the antihypertensive effects of propranolol (80 mg/day) for 1 day or for 2 weeks were evaluated in relation to the degree of beta-adrenoceptor blockade induced. A significant and similar fall in systolic blood pressure was observed after 1 day and 2 weeks on propranolol in both groups of patients. In contrast, diastolic blood pressure showed only a minor decrease after 1 day of therapy (-2 +/- 2 and -3 +/- 1 mm Hg) but a significant drop (-7 +/- 3 and -9 +/- 3 mm Hg) after 2 weeks in the mild and moderate hypertension groups, respectively. Plasma propranolol levels and decreases in resting heart rate and PRA were similar after 1 day and 2 weeks of treatment. Isoprenaline dose-response curves for systolic and diastolic blood pressure, heart rate and PRA showed similar parallel shifts after 1 day and 2 weeks of treatment. The effect of graded bicycle exercise on these parameters were also similarly blunted. These results indicate that over time, systolic blood pressure decreases rapidly whereas diastolic blood pressure shows a delayed fall following initiation of low-dose propranolol therapy, despite the same degree of beta-adrenoceptor blockade.

Assessment of beta-adrenergic blockade with propranolol in patients with cirrhosis.

Fourteen patients with cirrhosis and bleeding esophageal varices were treated with propranolol. The dose of propranolol was determined by decreasing the resting heart rate by 25% 12 hr after an oral dose of propranolol which was given twice a day. Significant decreases in the hepatic venous pressure gradient and cardiac output after 1 month of propranolol administration was observed. To assess beta-adrenergic blockade, the isoproterenol test and plasma propranolol levels were evaluated. Increasing doses of isoproterenol were injected to increase the resting heart rate 25 beats per minute (chronotropic dose 25 or CD25 ). Plasma propranolol concentrations were measured in blood samples drawn 4 hr after the last oral dose. The mean CD25 was 5 +/- 2 micrograms before and 146 +/- 84 micrograms after 1 month of propranolol administration. The plasma propranolol level after 1 month of drug administration was 0.69 +/- 0.47 microM per liter i.e. 2.33 +/- 1.59 micrograms per ml. A significant correlation was found between the CD25 measured after continuous propranolol administration and plasma propranolol level. In conclusion, the efficacy of beta-adrenergic blockade was estimated by the isoproterenol test which correlates with the plasma propranolol level in patients with cirrhosis. This study suggests that the isoproterenol test is useful in assessing beta-adrenergic blockade with propranolol in patients with cirrhosis.

Kinetic interactions of nadolol and propranolol with cimetidine.

British Journal of Clinical PharmacologyVolume 17, Issue 4 p. 486-487 Free Access Kinetic interactions of nadolol and propranolol with cimetidine. KL Duchin, KL DuchinSearch for more papers by this authorMA Stern, MA SternSearch for more papers by this authorDA Willard, DA WillardSearch for more papers by this authorDN McKinstry, DN McKinstrySearch for more papers by this author KL Duchin, KL DuchinSearch for more papers by this authorMA Stern, MA SternSearch for more papers by this authorDA Willard, DA WillardSearch for more papers by this authorDN McKinstry, DN McKinstrySearch for more papers by this author First published: April 1984 https://doi.org/10.1111/j.1365-2125.1984.tb02379.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Feely, J., Wilkinson, G. R. & Wood, A. J. J. (1981). Reduction of liver blood flow and propranolol metabolism by cimetidine. New Engl. J. Med., 304, 692– 695. Funke, P. T., Malley, M. F., Ivashkiv, E. & Cohen, A. I. (1978). Determinations of serum nadolol levels by GLC-selection monitoring mass spectrometry: comparison with a spectrofluoro-metric method. J. pharm. Sci., 67, 653– 657. Gibaldi, M. & Perrier, D. (1982). Pharmacokinetics. New York: Marcel Dekker, Inc. Kirch, W., Spahn, H., Kohler, H., Ohnhaus, E. E. & Mutschler, E. (1982). Interactions of metoprolol, propranolol, and atenolol with concurrent administration of cimetidine. Klin. Wochenschr., 60, 1401– 1407. Pelkonen, O. & Puurunen, J. (1980). The effect of cimetidine on in vitro and in vivo microsomal drug metabolism in the rat. Biochem. Pharmac., 29, 3075– 3080. Reimann, I. W., Klotz, U., Siems, B. & Frohlich, J. C. (1981). Cimetidine increases steady-state plasma levels of propranolol. Br. J. clin. Pharmac., 12, 785– 790. Shand, D. G., Nuckolls, E. M. & Oates, J. A. (1970). Plasma propranolol levels in adults with observations in four children. Clin. Pharmac. Ther., 11, 112– 120. Citing Literature Volume17, Issue4April 1984Pages 486-487 ReferencesRelatedInformation

An evaluation of a new patient compliance index using plasma propranolol levels

Propranolol levels in plasma were studied in relation to dose prescribed in order to assess poor compliance with antihypertensive treatment. Fifty consecutive ambulatory patients (36–81 years) having hypertension, including 19 with azotemia, were investigated. Patient interviews using questionnaires and chart reviews were used to evaluate compliance. A composite Compliance Index was calculated for each patient. Individual oral doses of propranolol ranged from 20 to 160 mg. Subsequent plasma levels were determined by high performance liquid chromatography. Good correlation between last oral dose (mg) per body weight (kg) and log plasma propranolol levels were observed in patients whose compliance indices were above the mean for this sample ( r = 0.74, p < 0.01), when blood pressure control was satisfactory ( r = 0.66) or excellent ( r = 0.78), and when serum creatinines were ⩾ 1.4 ( r = 0.76, p < 0.001). Poor correlations between dose and propranolol levels suggest poor compliance with treatment.

Propranolol effects on hypertension and the arterial wall beyond the treatment period in turkeys.

To determine if the effects of propranolol on hypertension and the arterial wall persisted for a significant time after the medication was discontinued, various parameters were compared at 16 weeks in control turkeys (CC), in birds on the medication from 3 days to 16 weeks (PP), and in others that were treated only from 3 days to 10 weeks (PC). At 16 weeks, arterial blood pressure, maximum rate of pressure increase (dp/dt max), and aortic intimal hyperplasia were lowest in the PP group, intermediate in the PC birds, and highest in the CC turkeys. Likewise, the vascular wall constituted 61% of the radius of the coronary arteries in the CC group, but only 52% and 45% in the PC and PP groups, respectively. At 16 weeks, heart rate was lowest and aortic tensile strength highest in the group that was treated for the entire period, at the end of which the average plasma propranolol level was 97 ng/ml. At the same age, heart rate and aortic tensile strength were approximately the same in the CC and PC groups, and propranolol was not detectable in the plasma. It is concluded that the administration of propranolol to hypertensive turkeys early in life reduced blood pressure, aortic intimal hyperplasia, and arterial wall thickness and that these effects persisted to a significant degree for at least 6 weeks after the medication was discontinued. The higher aortic tensile strength that was produced by propranolol did not persist.

Propranolol Infusion After Abdominal Surgery-Reply

In Reply.— We are grateful to Hug et al for their letter, their interest, and their corroboration of the usefulness of propranolol infusions in patients after surgery. We also want to apologize for failing to cite their previous abstract (their reference 1). Comparison of their protocol with ours shows similar average infusion rates, although their doses were prescribed on a body-weight basis, and we found average doses to work as well. Administration of the usual oral propranolol dose just before surgery, in our hands, obviated the need for a bolus IV dose after surgery before the institution of the constant infusion. However, if 12 hours or more has separated the last oral dose from initiation of constant IV therapy, an IV bolus would be worthwhile, as they point out, to reach equilibrium sooner. They measured plasma propranolol levels several times each hour for four to seven hours. In the interest

Combined effects of propranolol and ethanol on human psychomotor performance

Twelve male subjects were given placebo or 160 mg propranolol, in divided doses, during a 24-hr period before drinking a beverage containing 0 or 50 ml ethanol/70 kg body weight. Tests designed to measure mental and motor performance were administered 75 min after the last dose of propranolol. The tests performed included the wobble board (WB), pursuit meter (PM), delayed auditory feedback (DAF), pegboard (PB), tapping, time estimation (TE), and a modified Cornell medical index (CMI). A mean blood ethanol concentration of 48.0 ± 9.1 mg/dl and a mean plasma propranolol level of 33.1 ± 13.1 ng/ml were achieved. Ethanol alone significantly impaired performance in 12 out of 20 tests ( p < 0.05). Propranolol significantly ( p < 0.05) antagonized the decrement in psychomotor performance induced by ethanol on the PM. In all other tests, there was no significant interaction between ethanol and propranolol. Propranolol alone had no significant effect on the psychomotor tests. When the drugs were combined, the subjective symptoms, as measured by the CMI, showed a trend toward being additive. This study suggests that no adverse interaction occurs between therapeutic doses of propranolol and minimum impairment doses of ethanol.

Propranolol dosage, plasma concentration, and beta blockade.

One hundred sixty-nine normal men received varying propranolol dosage regimens and placebo. Dose level and frequency were compared with plasma propranolol levels and beta blockade, as assessed by reduction of exercise tachycardia. Propranolol levels above 20 ng/ml induced significant beta blockade. An average daily propranolol dose slightly in excess of 160 mg led to a minimum plasma level above 20 ng/ml. Approximately 50% of subjects achieved 20 bpm or greater decrease in exercise tachycardia with 160 mg per day. The degree of beta blockade at the daily minimum propranolol level was related to dose and not dose frequency. The relation of propranolol dose and plasma levels to beta blockade in normal subjects appears to reflect observations in large clinical trials.

Effects of cimetidine and ranitidine on steady-state propranolol kinetics and dynamics.

The influence of cimetidine (1000 mg daily, one day oral pretreatment) and ranitidine (300 mg daily by mouth, 1 and 6 days pretreatment) on steady-state propranolol (160 mg sustained-release capsule, once daily) plasma levels (Psss) and dynamic beta-blocker effects was assessed by bicycle ergometer exercise and isoproterenol sensitivity test in five normal subjects. During the 3 hr of the dynamic tests Psss were elevated from 25% to 67% by cimetidine, whereas Pss was unchanged by ranitidine. The estimated hepatic blood flow (EHBF) as calculated from indocyanine green (ICG) plasma clearance was only slightly reduced by 15 +/- 23% (mean +/- SD, n = 4) after one oral dose of 150 mg ranitidine and showed substantial intersubject variability. Dynamic parameters, like propranolol-induced heart rate and blood pressure changes under physical exercise or during the isoproterenol sensitivity test, were not influenced by ranitidine or cimetidine. Since our study was performed on normal subjects with relatively low propranolol doses these results do not rule out the risk of severe reinforcement of beta-adrenergic receptor blocking effects if propranolol and cimetidine are taken together by patients.

Altered jejunal surface pH in coeliac disease: its effect on propranolol and folic acid absorption.

1. Propranolol and folic acid absorption were studied separately in healthy subjects, non-coeliac patients and patients with treated and untreated coeliac disease. 2. The surface pH of jejunal biopsy samples was measured with a pH electrode. 3. When compared with values found in healthy subjects, plasma propranolol levels were elevated in coeliac disease and, in contrast, serum folic acid levels were depressed after oral administration of the drug. Jejunal surface pH was more alkaline in the coeliac groups than in the healthy and non-coeliac subjects. 4. Pharmacokinetic analysis of the plasma drug levels allowed evaluation of the rate constants associated with absorption and elimination. The absorption rate constant was decreased for folic acid in the coeliac group, but increased for propranolol. These changes correlated with variation in surface pH. 5. Although the changes in drug disposition in treated and untreated coeliac disease are the result of several factors, it is suggested that jejunal surface pH may affect the rate of absorption and therefore the plasma concentration-time profile of drugs which undergo dissociation.

Plasma levels of (+) and (−)−propranolol and 4‐hydroxypropranolol after administration of racemic (+/‐)‐propranolol in man.

1 We have given fifteen healthy volunteers single doses of racemic (+/-)-propranolol orally (40 mg) and intravenously (5-10 mg) to find out how large the variation was of the ratio between (-)- and (+)-propranolol plasma levels in relation to that of total levels of propranolol and 4-hydroxypropranolol. 2 Total propranolol (+/-)-levels 2 h after a 40 mg oral dose of (+/-)-propranolol varied from 21 to 580 nmol/l and those of 4-hydroxypropranolol from 0 to 33 nmol/l. Their levels did not correlate. The ratio between (-)- and (+)-propranolol levels varied from 0.99 to 2.04. The plasma half-lives of the two isomers were usually similar. 3 We conclude that in most single doses studies on relationships between plasma concentrations and effects (beta-adrenoceptor blockade) it is not necessary to quantitate (+)- and (-)-propranolol levels separately since total (+/-) plasma propranolol levels varied much more than the ratio between (-)- and (+)-propranolol.

Intravenous propranolol in patients with inflammation.

British Journal of Clinical PharmacologyVolume 13, Issue 4 p. 577-578 Free Access Intravenous propranolol in patients with inflammation. DG Waller, DG WallerSearch for more papers by this authorCL Smith, CL SmithSearch for more papers by this authorAG Renwick, AG RenwickSearch for more papers by this authorCF George, CF GeorgeSearch for more papers by this author DG Waller, DG WallerSearch for more papers by this authorCL Smith, CL SmithSearch for more papers by this authorAG Renwick, AG RenwickSearch for more papers by this authorCF George, CF GeorgeSearch for more papers by this author First published: April 1982 https://doi.org/10.1111/j.1365-2125.1982.tb01426.xCitations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES De LEVE, L.D. & PIAFSKY, K.M. (1981). Pharmacokinetic consequences of variation in plasma propranolol binding due to rheumatoid arthritis. Clin. Pharmac. Ther., 29, 239– 240. McDEVITT, D.G., FRISK-HOLMBERG, M., HOLLIFIELD, J.W. & SHAND, D.G. (1976). Plasma binding and the affinity of propranolol for the beta receptor in man. Clin. Pharmac. Ther., 20, 152– 157. NATION, R.L., PENG, G.W. & CHIOU, W.L. (1978). High pressure liquid chromatographic method for the simultaneous quantitative analysis of propranolol and 4-hydroxy propranolol in plasma. J. Chromatog., 145, 429– 436. PARSONS, R.L., KAYE, C.M., RAYMOND, K., TROUNCE, J.R. & TURNER, P. (1976). Absorption of propranolol and practolol in coeliac disease. Gut, 17, 139– 143. PIAFSKY, K.M., BORGA, O., ODAR-CEDERLOF, I., JOHANSSON, C. & SJOQVIST, F. (1978). Increased plasma protein binding of propranolol and chlor-promazine mediated by disease-induced elevations of plasma aracid glycoprotein. New Engl. J. Med., 299, 1435– 1439. SCHNEIDER, R.E., BABB, J., BISHOP, H., MITCHARD, M., HOARE, A.M. & HAWKINS, C.F. (1976). Plasma levels of propranolol in treated patients with coeliac disease and patients with Crohn's disease. Br. med. J., 2, 794– 795. SCHNEIDER, R.E., BISHOP, H. & HAWKINS, C.F. (1979). Plasma propranolol concentrations and the erythrocyte sedimentation rate. Br. J. clin. Pharmac., 8, 43– 47. Citing Literature Volume13, Issue4April 1982Pages 577-578 ReferencesRelatedInformation

The use of long-acting propranolol ('Inderal' LA) in the management of elderly hypertensive patients.

Fifteen elderly patients whose hypertension was controlled by conventional propranolol 80 mg twice a day had their medication changed to one capsule of 'Inderal' LA (160 mg) daily. The blood pressure, heart rate and propranolol concentrations were measured at various time points when the patients were receiving the conventional preparation and these assessments were repeated when the long-acting preparation was administered. Although the heart rate was lower with conventional propranolol than with 'Inderal' LA there was no significant difference in the blood pressure levels. The mean peak blood level of propranolol was, however, significantly lower with 'Inderal' LA compared with conventional propranolol and occurred later. At 12 h the plasma propranolol levels were higher after 'Inderal' LA then following the intake of conventional propranolol (p less than 0.01); there was no difference in the plasma levels at 24 h. The area under the concentration time curve was significantly higher on conventional propranolol. Compared with published data, the plasma levels were higher than those in younger patients. 'Inderal' LA was well tolerated and side effects were minimal.

Influence of Surgery on Plasma Propranolol Levels and Protein Binding

The influence of surgery and anesthesia on perioperative plasma propranolol levels was studied in 25 hyperthyroid and five euthyroid patients undergoing thyroidectomy. Propranolol levels fell markedly after surgery as a consequence of poor drug administration in the immediate postoperative period due largely to patients' nausea and inability to swallow. Propranolol was not detectable in the plasma of three hyperthyroid patients 8 hr after surgery. When propranolol was given through a nasogastric tube, propranolol levels were satisfactory throughout. Compared with preoperative levels, in all patients there was a two- to threefold rise in total and free propranolol levels 24 hr after surgery, suggesting decreased hepatic clearance of propranolol. The degree of plasma protein binding of propranolol had also increased on the day after surgery, leading to a 30% reduction in propranolol free fraction. Surgery and anesthesia greatly influence the handling of propranolol in the perioperative period. Clinical Pharmacology and Therapeutics (1980) 28, 759–764; doi:10.1038/clpt.1980.232

Combined High-performance Liquid Chromatographic Procedure for Measuring 4-hydroxypropranolol and Propranolol in Plasma: Pharmacokinetic Measurements Following Conventional and Slow-Release Propranolol Administration

An assay is described for the simultaneous determination of propranolol and its active metabolite, 4-hydroxypropranolol, in human plasma. Both compounds were separated from an ethereal extract by high-performance liquid chromatography employing a C18 bonded-phase column. Detection of the effluent was by fluorescence. Suitable fluorescent spectrometers and wavelength settings that allow optimum detection of both compounds have been described. The limit of sensitivity was 2 ng/ml for both propranolol and 4-hydroxypropranolol. Mean peak plasma levels of propranolol and 4-hydroxypropranolol in six patients receiving a single dose of a slow-release 160-mg formulation of propranolol were 28 and 6 ng/ml, respectively. These levels were about one-tenth the level obtained following a single conventionally prepared dose of propranolol (160 mg). Peak levels were delayed and plasma levels of propranolol persisted for a longer period with the slow-release formulation. Area under the curve estimates suggested that the bioavailability of the slow-release formulation following single-dose administration was about one-third that of the conventional preparation.

Propranolol and sotalol metabolism after a drinking party.

The effects of alcohol consumed during an evening party on the metabolism and response of beta-adrenergic blocking drugs were investigated in healthy subjects. The drugs were given 12 hr after the first drink. The plasma clearance rate of propranolol, metabolized in the liver, increased, while that of sotalol, which is eliminated unchanged, was reduced. Plasma propranolol levels, but not those of sotalol, were related to blood alcohol content. The blood pressure-reducing effect of propranolol diminished after alcohol and that of sotalol increased. Both drugs reduced the heart rate after alcohol although they were unable to cancel out entirely the alcohol-induced increase in the heart rate. The results show that drinking may alter the metabolism of beta-blocking drugs. Drinking habits must be considered in therapy with beta-blocking drugs or when seeking reasons for angina pectoris or arterial hypertension that does not respond to therapy.

Myocardial Sensitivity to Isoproterenol Following Abrupt Propranolol Withdrawal in Conscious Dogs

The sensitivity of the cardiovascular system to isoproterenol following abrupt cessation of propranolol administration was studied in chronically instrumented conscious dogs pretreated orally with propranolol for 14 days. The effects of intravenous isoproterenol on heart rate, blood pressure, and mean velocity of circumferential fiber shortening (Vcf) were determined before and during propranolol administration and then at 12 hr intervals following drug withdrawal. During propranolol administration, all dose-response curves to isoproterenol were predictably shifted to the right. Twenty-four hours following propranolol withdrawal, when plasma levels of drug averaged only 7 ng/ml, the chronotropic response to isoproterenol remained significantly inhibited. In contrast, the Vcf response recovered rapidly and at 24 hr equaled the pretreatment control response. Furthermore, between 36 and 60 hr, when plasma propranolol levels averaged less than 1 ng/ml, the Vcf dose-response curve to isoproterenol was shifted to the left of control prior to returning to the pretreatment level. This leftward displacement of the Vcf response curve was not accompanied by a parallel change in the heart rate response or in afterload. Plasma norepinephrine levels were measured throughout the study and were not altered during drug treatment or following withdrawal. Thus, the data indicate that abrupt cessation of propranolol administration is associated with a period of increased myocardial sensitivity to at least the inotropic effects of isoproterenol and that abrupt withdrawal does not result in acute changes in sympathetic nervous system activity.

Essential tremor treated with propranolol: lack of correlation between clinical effect and plasma propranolol levels.

Five patients with essential tremor were treated with increasing daily doses of propranolol. Tremor intensity was assessed after each propranolol dose had been given daily for a period of at least seven days. The evaluation was made 12 to 15 hours after the last propranolol ingestion. It included a semiquantitative clinical tremor evaluation and quantitative registration with an accelerometer. Electronic integration of the accelerometer curves gave an arbitrary measure of tremor intensity. Plasma propranolol concentration was determined at each tremor measurement. The reduction in tremor correlated with increasing propranolol doses, whereas plasma propranolol concentrations varied widely among individuals and could not be correlated with tremor reduction. Most of the patients had considerable diminution in tremor at low propranolol doses, often with an unmeasurable plasma propranolol concentration. Determination of plasma concentrations has little value in long-term treatment of essential tremor with propranolol. The dosage can be sufficiently guided by clinical evaluation of effect.