Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol

Abstract

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.Methods: Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm.Results: The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value<0.001).Conclusion: This study has confirmed that the pharmacokinetic differences are not able to justify over-responsiveness of Iranian population 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.

Propranolol decreases DRD3 and SLC1A2 gene expression in patients with essential tremor

“…There are different studies in the literature about the effect of propranolol on genes. (32) The mechanisms underlying the properties of propranolol in gene expression are unclear at present. To explain these mechanisms more comprehensive investigations (in vivo and in vitro) should be carried out with different doses of propranolol and the protein levels in 3D cultures should be determined in future.…”

Association of β1 and β2-adrenoceptor Polymorphisms With the Demand of Inotropic Catecholamine Support Following Coronary Artery Bypass Grafting in Iranian Population

“…A study done by Leineweber et al, 2007, in sample of German population showed that less post-surgical inotropic support is required in patients undergoing CABG who were preoperatively chronically treated with metoprolol and homozygous for the Arg389-β 1 AR, than those with one or two Gly389-β 1 AR alleles [14]. Over-responsiveness to propranolol has been reported in Iranian population that may be associated with polymorphism of β-adrenoceptors [15]. Furthermore, it was observed that Arg16Gly-β 2 AR genotype may have protective effect for hypertension in comparison with Arg16Arg-β 2 AR variant in Iranian population [16].…”