Research Article: Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol

Date Published: June 30, 2017

Publisher: Tabriz University of Medical Sciences

Author(s): Ebrahim Salehifar, Shima Ebrahim, Mohammad-Reza Shiran, Fatemeh Faramarzi, Hossein Askari Rad, Razieh Avan, Asadollah Mohseni Kiasari, Pouneh Ebrahimi.


Purpose: Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not.

Partial Text

Propranolol is a nonspecific beta-blocker that was presented as the first beta blocker in 1960.1 It is used in various cases, and mainly to treat high blood pressure,2 cardiac arrhythmias,3,4 thyrotoxicosis,5 migraine headaches,6 and psychiatric diseases.7 In recent studies, the beneficial effects of the drug to inhibit angiogenesis,8 treatment of different types of cancer,9-12 and hemangioma in children13 has been established. The dosage range of propranolol is very broad and the maintenance dose and maximum dose listed in reference books are much higher than the usual dose in our patients. For example, the recommended dose of propranolol at the beginning of the treatment of hypertension is mentioned to be 80 milligrams per day and the gradual increase to the maintenance dose of 80-320 mg per day.14 Many complications such as hypotension, bradycardia, depression, fatigue, sexual disorders and weight gain have been reported after taking beta blockers so the drug at the proper dose is necessary.15,16 Despite the widespread use of propranolol, the suitable dosage range is not clear in Iranian population. It is believed that our patients are not able to tolerate high dosage of propranolol that is mentioned in the references. It seems that the intensification of pharmacodynamic effects of the drug, especially bradycardia or hypotension prevents prescribing a standard dose of the medication. The mean pharmacokinetic parameters of propranolol in healthy volunteers in previous studies, (clearance equal to 0.96‏ ±0.3 Lit/kg/hr, the volume of distribution equal to 4.3‏ ±0.6 Lit/kg, half-life equal to 3.4 ±0.4 (hour) and oral bioavailability equal to 26±10%), has been declared.17,18 Given the uncertainty of pharmacokinetic parameters of propranolol in our population, this study was conducted to determine pharmacokinetic parameters of propranolol in a sample of healthy volunteers of Iranian population.

This study was conducted on 20 healthy volunteers (10 men) at the Fatemeh Zahra educational hospital of Mazandaran University of Medical Sciences. Each subject gave his or her written informed consent to participation in the study, which was approved by the Research Ethics Committee of Mazandaran University of Medical Sciences (approval number 2.3.84-458).

The demographic characteristics of volunteers in present study are summarized in Table 1. There were no significant differences in the characteristics of patients between males and females (independent sample t-test), except for weight, and height (p =≥0.046). The weight and height were significantly higher in males than in females (p<0.001). According to the results of this study, it seems that pharmacokinetic differences are not able to explain over-responsiveness of our patients to propranolol. Pharmacodynamic differences in responding to beta blocker drugs by Renin secretion or having a different sensibility to beta receptors might play a role in making our population have a different response to propranolol. This study was an approved research project sponsored by Deputy of Research and Technology, Mazandaran University of Medical Sciences, to which the authors express their appreciation and thanks. We also declare our acknowledgment to the personnel of Fatemeh Zahra Hospital Laboratory as well as to all of the volunteers participated in this study. The approval number of the study was 2.3.84-458. The ethical standards were met according to Fifth revision of Declaration of Helsinki. The authors report no conflicts of interest.   Source:


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