Saliva Versus Plasma Bioequivalence of Azithromyci

Authors: Nasir Idkaidek Tawfiq Arafat Hazim Hamadi Salim Hamadi Ibrahim AlAdham

Publish Date: 2017/01/10

Volume: 17, Issue: 1, Pages: 219-224

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Abstract

A pilot openlabel twoway crossover bioequivalence study was done and involved a single 500mg oral dose of azithromycin given to eight healthy subjects under fasting conditions followed by a 3week 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 noncompartment analysis using WinNonlin V52 Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel PKSim V56 was used to estimate the effective intestinal permeability of azithromycinNo statistical differences were shown in area under the concentration curves to 72 h AUC0–72 maximum measured concentration C max and time to maximum concentration T max between test and reference azithromycin products P  005 in the saliva matrix and in the plasma matrix Due to the high intrasubject variability and low sample size of this pilot study the 90 confidence intervals of AUC0–72 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 229 and 233 respectively The mean ± standard deviation ratios of saliva/plasma of AUC0–72 C max and T max for test were 265 ± 159 151 ± 049 and 185 ± 14 while for the reference product they were 337 ± 220 157 ± 077 and 26 ± 127 respectively A good correlation of R = 087 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 usedSalivary excretion of some drugs has been reported previously as a good indicator for drug bioavailability therapeutic drug monitoring 1 2 3 4 5 6 pharmacokinetics 7 8 9 10 11 and also drug abuse 12 Saliva sampling offers a simple noninvasive and cheap method as compared 13 14 15 16 with plasma sampling yet needs special attention so that no drug residue is left in the mouth after dosing According to the Salivary Excretion Classification System SECS class I drugs of high intestinal permeability and low protein binding such as paracetamol are subjected to salivary excretion Class II drugs of low permeability and low protein binding such as metformin are subjected to salivary excretion since low permeability is counterbalanced by low protein binding Class III drugs of high intestinal permeability and high protein binding such as cinacalcet are subjected to salivary excretion since high protein binding is counterbalanced by high permeability Class IV drugs of low intestinal permeability and high protein binding such as montelukast are not subjected to salivary excretion 1 In addition drug analysis in the clean saliva matrix is simple and can be done using the same method of analysis as plasma matrix Azithromycin is a semisynthetic 15member azalide antibiotic derived from erythromycin It is characterized by better acid stability associated with more reliable and greater oral bioavailability more extensive tissue penetration and significantly longer elimination halflife compared with erythromycin Azithromycin is effective against Grampositive and Gramnegative pathogens Azithromycin is commonly used for the treatment and prophylaxis of respiratory tract infection skin and soft tissue infection and sexually transmitted diseases 17 18

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