Pharmacokinetic and Pharmacodynamic Study of Terazosin in Healthy Chinese Volunteers: Significant Hysteresis Phenomenon

Guifen Qiang,Man Yang,Yanan Zhang

doi:10.4172/jbb.1000091

Abstract

Aim: The present study investigated the correlation between plasma concentration and antihypertensive effect of terazosin in healthy Chinese volunteers. Methods: A randomized, single-dose pharmacokinetic study of 2 mg terazosin hydrochloride tablet was conducted in healthy Chinese male subjects. Supine blood pressure and heart rate were measured before and after dosing, using cardiogram monitor. Serial blood samples were collected and plasma concentrations of terazosin were quantified by high performance liquid chromatography (HPLC) with a fluorescence detector. Non-compartmental pharmacokinetic analysis was applied to plasma concentrations. Results: Plasma concentration of terazosin reached to peak concentration at 0.89±0.62 hours (T max ), and then decreased with half-life value of 10.21±1.41 hours. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased from 0.25 hours till 24 hours after dosing. The maximum decrease of 8.5±5.3 mmHg (7.78%) in SBP ( P <0.05) and 12.9±6.0 mmHg (19.82%) in DBP ( P <0.001) occurred at 8 hours after dosing with a lagging time of 7 hours than T max , different from 1.2-1.8 hours of lagging time in healthy Spanish subjects. The heart rate increased from 0.25 hours till 24 hours with the maximum increase of 14.3±7.8 beats/min (23.85%) at 6 hours after dosing. Conclusion: The findings suggested that terazosin had a significant hysteresis phenomenon of antihypertensive effect behind plasma concentration of terazosin in healthy Chinese subjects, as was different from other racial subjects

Highlights

Terazosin, a post-synaptic α1-adrenoceptor antagonist, is used to treat the essential hypertension and the symptom of benign prostatic hyperplasia (BPH) [1,2]
Alfuzosin and tamsulosin, terazosin is the drug with a favorable effect in four areas of interest, including BPH symptoms, blood pressure, platelet aggregation, and endothelial functions in the patients with BPH [3]
It is worth noting that syncope and orthostatic hypotension, as serious adverse events, are prone to occur after the first dose of terazosin, namely “first-dose” effect [8]

Summary

Introduction

A post-synaptic α1-adrenoceptor antagonist, is used to treat the essential hypertension and the symptom of benign prostatic hyperplasia (BPH) [1,2]. Alfuzosin and tamsulosin, terazosin is the drug with a favorable effect in four areas of interest, including BPH symptoms, blood pressure, platelet aggregation, and endothelial functions in the patients with BPH [3]. Terazosin monotherapy or in combination with other antihypertensive agents significantly reduces the blood pressure, especially diastolic blood pressure in the patients with mild to moderate hypertension [1,6]. The maximum antihypertensive response (Emax) to terazosin was10.7 mmHg for SBP and 8.0 mmHg for DBP in the patients with mild to moderate essential hypertension [1]. Terazosin can decrease the blood pressure in healthy subjects. A single 0.5 mg terazosin can decrease the supine and 50°tilt DBP, while higher doses were required to decrease SBP in healthy Japanese volunteers [7]. It is worth noting that syncope and orthostatic hypotension, as serious adverse events, are prone to occur after the first dose of terazosin, namely “first-dose” effect [8]

Objectives

Methods

Results

Conclusion