Drug Res (Stuttg)
DOI: 10.1055/s-0043-117775
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Saliva versus Plasma Bioequivalence of Valsartan/Hydrochlorothiazide in Humans: Validation of Classes II and IV Drugs of the Salivary Excretion Classification System

Nasir Idkaidek1, Haneen Agha1, Tawfiq Arafat1
  • 1University of Petra, College of Pharmacy, Amman, Jordan
Further Information

Publication History

received 14 May 2017

accepted 26 July 2017

Publication Date:
28 August 2017 (eFirst)

Abstract

Aim The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS).

Methods Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6.

Results and Discussion Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn’t appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96–0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used.