Pharmacokinetics of propranolol and sotalol in hyperthyroidism

Summary The elimination and bioavailability of two beta-blocking agents, propranolol and sotalol, were studied in 10 thyrotoxic patients, both before and after treatment with iodine-131. Each subject received in random order propranolol 160 mg and sotalol 160mg as single oral doses both while hyperthyroid and after euthyroidism had been achieved. The pharmacokinetics of sotalol was not affected by hyperthyroidism, whereas serum propranolol concentrations were significantly lower during hyperthyroidism than in the euthyroid state. During hyperthyroidism, the bioavailability of propranolol was significantly reduced (p<0.05) and its clearance was increased (p<0.005), whereas there was no difference in its serum t_1/2. This indicates that the bioavailability of propranolol in hyperthyroidism is reduced by a mechanism which may depend on increased first-pass metabolism in the liver, or on an increased distribution volume of the drug. Both propranolol and sotalol caused a slight decrease in serum tri-iodothyronine concentration. As the effects of beta-blocking agents on the symptoms of hyperthyroidism are correlated with the serum concentration of the drugs, sotalol, with its long half-life and unaltered elimination in hyperthyroidism, has certain advantages over propranolol in the treatment of thyrotoxicosis.     

Nonlinear accumulation of propranolol enantiomers.

The accumulation of (+)- and (-)-propranolol was investigated in nine subjects who received 160 mg of racemic propranolol as a single dose and then once daily for 7 days. The serum concentrations of propranolol enantiomers were measured by h.p.l.c. using a novel chiral stationary phase allowing direct resolution of underivatized propranolol. The (+)-propranolol AUC increased from 412 +/- 223 ng ml-1 h after single doses (0-infinity) to 584 +/- 279 ng ml-1 h at steady-state (0-24 h) (P less than 0.05). Similarly, (-)-propranolol AUC increased from 609 +/- 304 to 777 +/- 370 ng ml-1 h (P less than 0.05). The AUC ratio (-)/(+) was 1.52 +/- 0.36 and 1.32 +/- 0.17 after single doses and steady-state, respectively (P greater than 0.05). Therefore, nonlinear accumulation occurs with both enantiomers although there is a trend for the (-)/(+) ratio to decrease at steady-state.     

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

1. The kinetics and dynamics of long acting propranolol 80 mg and 160 mg were examined after single oral doses to 12 healthy volunteers. 2. Long acting propranolol 160 mg produced a twofold increase in mean peak blood propranolol concentration and AUC compared with the lower dose. There was no difference in elimination half-life, bioavailability and mean residence time of propranolol between the two doses. 3. Resting pulse rate was decreased by long acting propranolol 160 mg but not by the lower dose. 4. Both preparations blocked exercise induced tachycardia during the entire observation period of 29 h. Percentage inhibition of exercise tachycardia was significant at all time points but long acting propranolol 160 mg exhibited a greater reduction at 24 h and 29 h. 5. Increase in systolic blood pressure during exercise was inhibited by both preparations during the entire observation period with no differences between them. 6. The doubling of the dose administered was reflected in blood concentrations but not in pharmacodynamic parameters. Few pharmacodynamic differences were found between the two doses.     

Nonlinear pharmacokinetics of unbound propranolol after oral administration

After multiple oral doses, propranolol has been reported to accumulate to a greater degree than expected based on its terminal elimination rate constant and dosage interval. To determine whether the decrease in presystemic elimination can be attributed solely to a decrease in unbound intrinsic clearance or possibly a decrease in unbound fraction, we studied the pharmacokinetics of unbound propranolol in nine healthy subjects who were given 160 mg of regular or sustained-release propranolol orally as single doses, and once daily for 7 d. Unbound propranolol concentrations were calculated by HPLC and equilibrium dialysis on each serum sample. With regular propranolol, the mean unbound oral clearance (CLoral) decreased 29%, from 503 +/- 281 after a single dose to 359 +/- 143 mL/min/kg at steady state (p less than 0.05). Similarly, CLoral decreased 33% with sustained-release propranolol from 1077 +/- 514 to 721 +/- 385 mL/min/kg (NS). The corresponding accumulation ratios for regular and sustained-release propranolol were 1.39 +/- 0.49 and 1.61 +/- 0.81, respectively (NS). Therefore, the mean bioavailability of sustained-release relative to that of regular propranolol was 0.52 +/- 0.23 and 0.54 +/- 0.17 for single doses and at steady-state, respectively. The percent unbound of propranolol ranged from 6.8 to 14.0 with an average of 10.1. Neither the percent unbound nor alpha 1-acid glycoprotein (AAG) serum concentrations were statistically different between single and multiple doses. The binding ratio was significantly correlated to AAG concentration (r = 0.776, p less than 0.05). The data support a decrease in unbound intrinsic clearance of propranolol with no change in unbound fraction, leading to an increase in bioavailability at steady state.     

Relative bioavailability of oral sustained-release and regular-release oxprenolol tablets at steady-state

The relative bioavailability of a test sustained-release (SR) oxprenolol tablet against an approved regular-release (RR) tablet has been investigated at steady-state. In a randomized two-way crossover study, one tablet of 160 mg SR oxprenolol once every 24 h and one tablet of 80 mg RR oxprenolol once every 12 h were given to 12 healthy volunteers for 5 days. Blood samples were collected from each subject just prior to each dose-administration on days 1 through 4, and at scheduled time points on day 5 and analysed for oxprenolol concentration using HPLC. The SR tablet resulted in 42 per cent reduction in mean peak drug levels (p = 0.0341) and a statistically non-significant 14 per cent increase in mean trough levels (p = 0.8357) than the RR tablet. However it required 160 per cent longer time to reach average steady-state concentrations (Css) on day 5 (1.38 h for SR versus 0.53 h for RR; p = 0.0205). The mean area under the plasma drug concentration-time curve at steady state (AUC96-120) with the SR tablet was approximately 18 per cent lower than that observed with the RR tablet, and the degree of fluctuation (DF) was reduced by 30 per cent (2.81 for SR versus 4.11 for RR; p = 0.0069). On average, a single dose of SR tablet and two doses of RR tablets maintained the drug levels above a constant Css of 204.6 ng ml-1 for 7.88 and 7.65 h, respectively (p = 0.3513).     

A comparative pharmacokinetic study of conventional propranolol and long acting preparation of propranolol in patients with cirrhosis and normal controls.

1 Six male patients with alcoholic cirrhosis and seven normal control subjects were each given 80 mg twice daily of conventional propranolol for 1 week and 160 mg once daily of a long acting preparation (LA) of propranolol for 1 week. 2 Plasma propranolol levels were measured at regular intervals on the first and seventh days of both weeks and also following an acute intravenous infusion of 10 mg propranolol on a separate occasion. 3 After the single intravenous dose the elimination half-life tended to be prolonged in the cirrhotic group (median 7.15 h) compared with controls (median 2.92 h) (P = 0.055). 4 After multiple oral dosing with 80 mg twice daily of conventional propranolol the steady-state plasma concentration (Css), area under the curve (AUC tau), peak concentration (Cmax) and trough concentration (Cmin) were significantly higher in cirrhotic patients and the peak: trough ratio (Cmax/Cmin) was significantly lower than controls. 5 After multiple oral dosing with 160 mg LA once daily Cmin was significantly higher than Cmax/min significantly lower in cirrhotic patients; Css, AUC and Cmax were higher than controls but not statistically different. 6 Within both subject groups the bioavailability of 80 mg twice daily of conventional propranolol tended to be greater than 160 mg LA once daily. Cmax was significantly higher in both groups and Css higher in the cirrhotic group with conventional propranolol. 7 In the cirrhotic group the mean reduction in supine heart rate in the steady state was 31.8% with conventional 80 mg twice daily propranolol and 23.75% with 160 mg LA once daily.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioavailability of sustained release propranolol formulations

In this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation (‘Inderal’ LA), were compared with a conventional ‘Inderal’ tablet. Twelve healthy adult male volunteers received, on a cross-over basis, on three separate occasions, 160 mg oral doses of three formulations of ‘Inderal’. Bioavailability was based on concentration of propranolol in whole blood. The peak blood level and area under the propranolol blood level curve fell as the dissolution time increased. The half-lives of the three formulations were inversely proportional to their dissolution rates, those of the sustained release formulations being considerably longer than that of the conventional tablet. The 160 mg ‘Inderal’ tablet produced a rapid 90-fold decline over 24 h in propranolol blood levels following a high initial peak. By comparison both sustained release formulations showed a less rapid fall in systemic levels and gave higher blood levels at the end of 24 h and plateau values between 8 and 14 ng ml ^?1. The ‘Inderal’ LA sustained release formulation gave consistently higher propranolol blood levels than the clinical trial sustained release formulation. This result is in good agreement with their dissolution profiles. The lowering of the systemic bioavailability as the dissolution time increases is thought to be due to an increased metabolism of propranolol.     

Pharmacokinetic and Pharmacodynamic Comparison of Immediate-Release and Sustained-Release Adinazolam Mesylate Tablets After Single- and Multiple-Dose Administration

The effect of adinazolam release rate on psychomotor performance and sedation was assessed by administering 40 mg adinazolam mesylate immediate-release (CT) tablets, 60 mg sustained-release (SR) tablets, and placebo in a double-blind crossover study in 15 healthy male subjects. A separate panel of 16 subjects received the above single doses and multiple-dose regimens of 40 mg CT tablets every 8 hr and 60 mg SR tablets every 12 hr according to a crossover design. Psychomotor performance was assessed by digit symbol substitution test, card sorting tasks, and sedation ratings. Following single-dose administration, dose-corrected adinazolam and N-desmethyladinazolam (NDMAD) AUC values were equivalent for SR and CT tablets. Peak adinazolam and NDMAD levels were lower and occurred later for the SR tablets. Decrements in card sorting were 50 and 3% at 1 hr and 17 and 20% at 6 hr for the CT and SR tablets, respectively. Maximal sedation scores were lower for the SR tablets compared to the CT. Dose-corrected AUC was comparable between single and multiple doses for both adinazolam and NDMAD; no differences were observed in 24-hr AUC at steady-state between CT and SR tablets. Fluctuation ratios were reduced for both adinazolam and NDMAD following SR tablets. Psychomotor and sedative effects were attenuated upon multiple dosing. Thus, the reduction in peak plasma NDMAD following SR tablet administration results in a lesser sedation and psychomotor impairment on acute administration, and tolerance to these effects occurs on mulitiple dosing.     

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies

Two multiple dose crossover pharmacokinetic studies were carried out to determine the steady-state bioavailability of newly formulated generic propranolol HCl tablets relative to Inderal tablets. In Study I, 24 healthy volunteers were dosed with 4 x 10 mg test tablets, 1 x 40 mg test tablet, 4 x 10 mg Inderal tablets, and 40 mg of propranolol HCl in solution. In Study II, 24 healthy volunteers were dosed with 1 x 80 mg test tablet, 1 x 80 mg Inderal tablet, and 80 mg of propranolol HCl in solution. Both studies were of randomized design with each formulation administered every 8 h for 15 doses. Serial plasma samples were obtained for 8 h after morning doses on Days 4 and 5 of each treatment period and assayed for propranolol using a validated HPLC method. Mean plasma concentration-time data for test tablets and reference tablets were superimposable in both studies. Pharmacokinetic parameters from Days 4 and 5 were combined for statistical analysis since subjects were determined to have reached steady-state. Mean AUC, Cmax, tmax, and Cmin values were not statistically different between test tablets and Inderal tablets in either study. Based on these findings, the test tablets demonstrated the same rate and extent of propranolol absorption as did corresponding Inderal tablets. Therefore, the test tablets and Inderal tablets were determined to be bioequivalent.     

Pharmacokinetics and bioavailability of three dyphylline preparations

The pharmacokinetics and bioavailability of 3 oral dyphylline preparations, solution (S), regular (R) and sustained release (SR), were studied in 8 healthy subjects (mean age 25 years). A single dose of each preparation, 20 mg X kg-1, was given at one week intervals and multiple serum samples obtained over 24 h. Drug levels were measured by high performance liquid chromatography. No adverse effects were found. The dyphylline half-life for the solution was 2.16 +/- 0.18 h and for the tablet 2.59 +/- 0.56 h. The mean clearance rate for S was 13.6 +/- 1.7 h-1 and volume of distribution 43.0 +/- 3.91. Peak concentration (Cmax, micrograms X ml-1), time of peak (Tmax, h), area under the curve (AUC, micrograms X ml-1 X h) and relative bioavailability (RB, %), were determined for three preparations: Cmax S, 33.7 +/- 3.7; R, 27.7 +/- 4.2; SR, 10.4 +/- 1.5 Tmax: S, 0.33 +/- 0.0; R, 0.66 +/- 0.0; SR, 2.13 +/- 1.1 AUC: S, 108.4 +/- 12.1; R, 113.9 +/- 25.2; SR, 104.0 +/- 30.8 RB: Reference Product R, 105.00 +/- 16.00; SR, 100.00 +/- 25.00 The data confirm the short half-life of dyphylline, demonstrate a lack of toxicity for the 20 mg X kg-1 dose and establish bioequivalence for the products studied.     

Comparison of the activity and plasma levels of oxprenolol,slow release oxprenolol,long acting propranolol and sotalol

Summary Observations were made in 5 healthy subjects who exercised before and 1, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg long acting propranolol and 400 mg sotalol. Blood samples were obtained before and at 1, 2, 3, 6, 8, 10 and 24 h after drug administration and assayed for drug concentration. Although the plasma concentration of oxprenolol after S. R. oxprenolol was significantly less at 1 and 2 h and significantly greater at 24 h than after conventional oxprenolol, there was little difference between the effects of the two drugs on an exercise tachycardia. The plasma level of propranolol and the reduction in an exercise tachycardia after L. A. propranolol increased slowly to reach a peak at 6 h and then declined gradually to 24 h. The maximum plasma concentration and effect after sotalol occurred at 3 h and then declined with an elimination half-life of 12.1 h. At 24 h the percentage reduction in an exercise tachycardia was 8.3±2.5 after oxprenolol, 10.0±2.3 after S. R. oxprenolol, 18.0±3.2 after L. A. propranolol and 14.7±3.4% after sotalol.     

Decreased bioavailability of propranolol due to interactions with adsorbent antacids and antidiarrhoeal mixtures

The interaction of propranolol (50–160 mg/100 ml) with recommended doses of magnesium trisilicate, kaolin-pectin and bismuth subsalicylate suspensions was studied. Magnesium trisilicate and bismuth subsalicylate were found to adsorb propranolol with a limiting adsorptive capacity of 112 and 97 mg/g, respectively. Kaolin-pectin suspension adsorbed practically all of the drug. The effect of these interactions on the bioavailability of propranolol in rats was determined. The extent, but not the rate. of propranolol absorption was decreased on concomitant administration of the adsorbents. Peak propranolol plasma concentrations decreased by 292 5% and a parallel decrease of 35–44% in AUC values was observed. These interactions suggest possible clinically important differences in propranolol bioavailability.     

Influence of physical exercise on the pharmacokinetics of propranolol

Summary The pharmacokinetics of propranolol after oral and intravenous administration was studied at rest and on an exercise day in 8 healthy subjects. On the exercise day the subjects performed physical exercise for 7 h, consisting of bicycle ergometer exercise at 50% of maximal work capacity and outdoor walking. Propranolol (80 mg p.o., or 0.2 mg/kg body weight i.v.) was administered 30 min before the start of the exercise. After oral administration the terminal phase halflife, (t1/2) and area under the curve (AUC) were both significantly reduced on the exercise day compared to the rest day. The bioavailability of propranolol was reduced by prolonged physical exercise and plasma levels of propranolol were about 30% lower at the end of the exercise day than at the end of the rest day. After intravenous administration, t1/2 was also reduced on the exercise day as compared to the rest day. AUC, clearance and volume of distribution did not differ on the two days. On the other hand, indocyanine green (ICG) clearance was significantly reduced during the bicycle ergometry periods on the exercise day. The combination of reduced ICG clearance, suggesting a reduction in hepatic blood flow, and a decreased t1/2 and unchanged clearance of propranolol on the exercise day was unexpected.     

Sublingual and oral isoxsuprine in patients with Raynaud's phenomenon

Summary Plasma propranolol steady-state concentrations (Css) were measured in 24 hyperthyroid and 6 hypothyroid patients before and after correction of the thyroid disorder. Following treatment of hyperthyroidism by surgery, antithyroid drugs or radioiodine, there was a significant rise in the plasma propranolol Css in patients receiving propranolol either 160 mg/day, 240 mg/day, or 480 mg/day. In addition, in five patients the area under the plasma propranolol concentration versus time curve during a dosing interval increased significantly from 405 ng/ml/h when hyperthyroid to 778 ng/ml/h when euthyroid. In the hypothyroid patients given propranolol 160 mg/day concomitantly with 1-thyroxine therapy the plasma propranolol Css fell significantly when euthyroid. There was a small but significant increase in the degree of plasma protein binding of propranolol, following treatment of hyperthyroidism and a significant decrease following correction of hypothyroidism. It is concluded that thyroid disorders markedly influence propranolol handling.     

Pharmacokinetics of l-propranolol during repetitive dosing in normal and uranyl nitrate-induced renal failure rats

The effect of experimental renal failure on the intravenous and oral pharmacokinetics of l-propranolol was studied in rats. Renal failure was induced by a single intravenous injection of uranyl nitrate (5 mg/kg). Pharmacokinetic studies were carried out on the fifth day after injection of the renal toxin (renal failure group) or saline (control group). Serum concentration time course of l-propranolol was characterized after a single intravenous or oral dose as well as after five consecutive doses of the drug given at 3-hr intervals. During repetitive intravenous drug administration, steady state was reached by the second dose, i.e., within 6 hr after initiation of repetitive dosing. No significant difference in the serum concentration time course of l-propranolol was observed between control and renal failure animals. In both groups the AUC over the steady-state dosing interval was on the average 21-27% higher than the AUC after a single dose, indicating a slight decrease in the systemic clearance of l-propranolol during repetitive intravenous drug administration. An approximately two- to three-fold higher serum l-propranolol concentration was observed in renal failure animals as compared to the normal controls after both single or repetitive oral dosing. The apparent reduction in oral clearance probably reflected an inhibition of the hepatic first-pass metabolism of l-propranolol in the renal failure rat. An unexpectedly high and protracted accumulation of serum l-propranolol concentration was observed during repetitive oral drug administration. Continuing accumulation was still evident after the fifth oral dose, i.e., a period of 15 hr or approximately 10 half-lives. The mean AUC over the last dosing interval was 32.0 and 17.8 times higher than the predicted steady-state estimate based on single oral dose data for control and renal failure rats, respectively. The substantial reduction in the oral clearance during repetitive drug administration may be due to an auto-inhibition of l-propranolol metabolism.     

口服普萘洛尔在健康中国人药物动力学的性别差异(英文)

目的:确定口服普萘洛尔(Pro)的体内分布与代谢是否在健康中国人中存在性别二态性.方法:12名健康志愿者(6男,6女)口服单剂量Pro 80 mg,其血浆Pro浓度用HPLC荧光法检测,药物动力学参数用MCPKP软件计算.结果:女性的AUC和C_(max)分别比男性高74％和99％,相反,Cl_o和V_d却分别比男性低109％和120％.女性T_(1/2)较长,但和男性比无显著差异,其他药物动力学参数未发现明显性别差异.结论:中国女性比男性有一个较高的Pro口服生物利用度,部分归因于她们在服药后对Pro的整体清除率较低和表观分布容积较小.     

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations

The kinetics and dynamics (inhibition of exercise tachycardia) of two controlled-release preparations of propranolol (Elanolol and Inderal LA) were examined in six normal volunteers. Conventional propranolol (Inderal) was also studied for comparison purposes. As compared to conventional propranolol (120 mg), single doses of Elanol (120 mg) and Inderal LA (160 mg) produced a smoother serum level profile, with lower and delayed peak times. Dose-corrected AUC0-24 values were greater after Elanol than after Inderal LA (651 +/- 147 vs 402 +/- 159 ng ml-1 h, means +/- s.e. mean, P greater than 0.05). The profile of inhibition of exercise tachycardia mirrored closely that of the serum levels. At steady state, all regimens studied (Inderal 40 mg three times daily; Elanol 120 mg once daily; Inderal LA 160 mg once daily) ensured relatively sustained serum levels and a stable degree of pharmacological effect. Dose-corrected AUC0-24 values were 797 +/- 148 ng ml-1 h after Inderal, 908 +/- 113 ng ml-1 h after Elanol and 602 +/- 122 ng ml-1 after Inderal LA. The bioavailability of Inderal LA was significantly lower than that of the other preparations. These results demonstrate that long-acting formulations of propranolol can be developed which are not necessarily associated with reduced bioavailability secondary to enhanced first-pass metabolism.     

Triazolam kinetics: interaction with cimetidine, propranolol, and the combination

Nineteen healthy volunteers received a single 0.5-mg oral dose of triazolam on four occasions under the following conditions: (1) triazolam alone; (2) triazolam with cimetidine, 300 mg four times daily; (3) triazolam with propranolol, 40 mg four times daily; (4) triazolam with both cimetidine and propranolol. Triazolam kinetics were determined from multiple plasma concentrations measured during 24 hours after each dose. Compared with control, peak plasma triazolam concentration (Cmax) was significantly increased by cimetidine (5.4 versus 3.9 ng/mL), total area under the plasma concentration curve (AUC) increased (21.3 versus 16.1 ng/mL X hr), and oral clearance decreased (485 versus 668 mL/min). However triazolam half-life was not increased. During propranolol alone, triazolam Cmax (4.1 ng/mL), AUC (14.3 ng/mL X hr), and clearance (759 mL/min) did not differ significantly from control, whereas kinetic variables for triazolam with cimetidine plus propranolol were similar to those with cimetidine alone. Plasma free fraction for triazolam (17 to 18% unbound) did not differ significantly among the four treatment conditions. Mean steady-state plasma cimetidine concentrations during trials 2 and 4 were similar (1.04 versus .98 micrograms/mL), whereas plasma propranolol was significantly higher during cimetidine plus propranolol than with propranolol alone (47 versus 29 ng/ml, P less than .001). Thus cimetidine coadministration significantly inhibits triazolam clearance, causing increased triazolam AUC and Cmax, but without a prolongation in half-life. Propranolol itself does not impair triazolam clearance, nor does propranolol potentiate the inhibitory effect of cimetidine alone.     

Pharmacokinetic evaluation of conventional and controlled release dosage form of propranolol

A comparative pharmacokinetic study of a new controlled release multiple unit propranolol formulation and a conventional propranolol tablet was carried out in twelve healthy human volunteers in a randomized balanced crossover design. Under a single dosage regimen, subjects were administered either a single capsule containing controlled release propranolol equivalent to 160 mg of the drug or 80 mg of conventional propranolol tablet, twelve hourly. Peak plasma propranolol concentrations were low which occurred later after controlled release administration than after the administration of the conventional tablet. Analysis of the area under the plasma concentration-time curve (AUC) for the two formulations indicate no significant difference of bioavailability despite a prolonged absorption time and maintenance of effective plasma concentration for the controlled release preparation.     

The interaction between propranolol and the novel antimigraine agent zolmitriptan (311C90)

Aims Zolmitriptan (Zomig, formerly known as 311C90), a selective 5HT_1B/1D agonist is under development as an acute oral treatment for migraine. Despite the use of prophylactic medication, such as propranolol, breakthrough attacks often occur in patients. Consequently we investigated the effects of propranolol on the pharmacokinetics of, and cardiovascular responses to, zolmitriptan.
Methods A double-blind, randomized, crossover study of the effects of pre-treatment with propranolol 160  mg daily for 7 days or placebo on the pharmacokinetics and effects on blood pressure of a single 10  mg dose of zolmitriptan in 12 healthy volunteers.
Results Propranolol increased mean zolmitriptan C _max and AUC by 56% and 37% respectively; mean t _1/2 was prolonged from 3.1 to 4.0  h. Mean C _max and AUC of the pharmacologically active N -desmethyl metabolite were reduced by 24% and 11% respectively and the metabolite:parent AUC ratio (AUC_m/AUC_p ) fell from 0.46 to 0.26. Mean C _max and AUC for the inactive indole acetic acid metabolite were both reduced by 13% and AUC_m/AUC_p from 1.04 to 0.59. A small pressor effect of short duration was observed following zolmitriptan with mean peak rises of 13 and 11  mmHg in systolic and diastolic pressures respectively; propranolol had no effect on the pressor response.
Conclusions The results suggest that propranolol inhibits biotransformation of zolmitriptan but with no change in the small pressor response to zolmitriptan. It is therefore unlikely that the pharmacokinetic changes will lead to clinically important changes in pharmacological effects and dosage adjustment of zolmitriptan is not required in patients taking propranolol for migraine prophylaxis.