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Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System
AIM: The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS). METHODS: A pilot, open-label, two-way crossover bioequivalence study was done, and invo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318338/ https://www.ncbi.nlm.nih.gov/pubmed/28074334 http://dx.doi.org/10.1007/s40268-016-0170-8 |
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author | Idkaidek, Nasir Arafat, Tawfiq Hamadi, Hazim Hamadi, Salim Al-Adham, Ibrahim |
author_facet | Idkaidek, Nasir Arafat, Tawfiq Hamadi, Hazim Hamadi, Salim Al-Adham, Ibrahim |
author_sort | Idkaidek, Nasir |
collection | PubMed |
description | AIM: The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS). METHODS: A pilot, open-label, two-way crossover bioequivalence study was done, and involved a single 500-mg oral dose of azithromycin given to eight healthy subjects under fasting conditions, followed by a 3-week washout period. Blood and unstimulated saliva samples were collected over 72 h and deep frozen until analysis by a validated liquid chromatography with mass spectroscopy method. The pharmacokinetic parameters and bioequivalence metrics of azithromycin were calculated by non-compartment analysis using WinNonlin V5.2. Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel. PK-Sim V5.6 was used to estimate the effective intestinal permeability of azithromycin. RESULTS AND DISCUSSION: No statistical differences were shown in area under the concentration curves to 72 h (AUC(0–72)), maximum measured concentration (C (max)) and time to maximum concentration (T (max)) between test and reference azithromycin products (P > 0.05) in the saliva matrix and in the plasma matrix. Due to the high intra-subject variability and low sample size of this pilot study, the 90% confidence intervals of AUC(0–72) and C (max) did not fall within the acceptance range (80–125%). However, saliva levels were higher than that of plasma, with a longer salivary T (max). The mean saliva/plasma concentration of test and reference were 2.29 and 2.33, respectively. The mean ± standard deviation ratios of saliva/plasma of AUC(0–72), C (max) and T (max) for test were 2.65 ± 1.59, 1.51 ± 0.49 and 1.85 ± 1.4, while for the reference product they were 3.37 ± 2.20, 1.57 ± 0.77 and 2.6 ± 1.27, respectively. A good correlation of R = 0.87 between plasma and saliva concentrations for both test and reference products was also observed. Azithromycin is considered a class I drug based on the SECS, since it has a high permeability and high fraction unbound, and saliva sampling could be used as an alternative to plasma sampling to characterize its pharmacokinetics and bioequivalence in humans when adequate sample size is used. |
format | Online Article Text |
id | pubmed-5318338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-53183382017-03-03 Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System Idkaidek, Nasir Arafat, Tawfiq Hamadi, Hazim Hamadi, Salim Al-Adham, Ibrahim Drugs R D Original Research Article AIM: The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS). METHODS: A pilot, open-label, two-way crossover bioequivalence study was done, and involved a single 500-mg oral dose of azithromycin given to eight healthy subjects under fasting conditions, followed by a 3-week washout period. Blood and unstimulated saliva samples were collected over 72 h and deep frozen until analysis by a validated liquid chromatography with mass spectroscopy method. The pharmacokinetic parameters and bioequivalence metrics of azithromycin were calculated by non-compartment analysis using WinNonlin V5.2. Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel. PK-Sim V5.6 was used to estimate the effective intestinal permeability of azithromycin. RESULTS AND DISCUSSION: No statistical differences were shown in area under the concentration curves to 72 h (AUC(0–72)), maximum measured concentration (C (max)) and time to maximum concentration (T (max)) between test and reference azithromycin products (P > 0.05) in the saliva matrix and in the plasma matrix. Due to the high intra-subject variability and low sample size of this pilot study, the 90% confidence intervals of AUC(0–72) and C (max) did not fall within the acceptance range (80–125%). However, saliva levels were higher than that of plasma, with a longer salivary T (max). The mean saliva/plasma concentration of test and reference were 2.29 and 2.33, respectively. The mean ± standard deviation ratios of saliva/plasma of AUC(0–72), C (max) and T (max) for test were 2.65 ± 1.59, 1.51 ± 0.49 and 1.85 ± 1.4, while for the reference product they were 3.37 ± 2.20, 1.57 ± 0.77 and 2.6 ± 1.27, respectively. A good correlation of R = 0.87 between plasma and saliva concentrations for both test and reference products was also observed. Azithromycin is considered a class I drug based on the SECS, since it has a high permeability and high fraction unbound, and saliva sampling could be used as an alternative to plasma sampling to characterize its pharmacokinetics and bioequivalence in humans when adequate sample size is used. Springer International Publishing 2017-01-10 2017-03 /pmc/articles/PMC5318338/ /pubmed/28074334 http://dx.doi.org/10.1007/s40268-016-0170-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Article Idkaidek, Nasir Arafat, Tawfiq Hamadi, Hazim Hamadi, Salim Al-Adham, Ibrahim Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System |
title | Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System |
title_full | Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System |
title_fullStr | Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System |
title_full_unstemmed | Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System |
title_short | Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System |
title_sort | saliva versus plasma bioequivalence of azithromycin in humans: validation of class i drugs of the salivary excretion classification system |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318338/ https://www.ncbi.nlm.nih.gov/pubmed/28074334 http://dx.doi.org/10.1007/s40268-016-0170-8 |
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