Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans

Aims: To study the pharmacokinetics of selected drugs in plasma and saliva matrixes in healthy human volunteers, and to suggest using non-invasive saliva sampling instead of plasma as a surrogate in bioavailability and bioequivalence (BA/BE) studies. Methods: Four different pilot BA/BE studies were...

Full description

Bibliographic Details
Main Author: Nasir M. Idkaidek
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:Saudi Pharmaceutical Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319016416301074
id doaj-13368f4a0a8045ad85dc3fafa5435699
record_format Article
spelling doaj-13368f4a0a8045ad85dc3fafa54356992020-11-24T23:54:15ZengElsevierSaudi Pharmaceutical Journal1319-01642017-07-0125567167510.1016/j.jsps.2016.10.002Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humansNasir M. IdkaidekAims: To study the pharmacokinetics of selected drugs in plasma and saliva matrixes in healthy human volunteers, and to suggest using non-invasive saliva sampling instead of plasma as a surrogate in bioavailability and bioequivalence (BA/BE) studies. Methods: Four different pilot BA/BE studies were done in 12–18 healthy humans. Saliva and plasma samples were collected for 3–5 half life values of metformin, tolterodine, rosuvastatin, and paracetamol after oral dosing. Saliva and plasma samples were assayed using LC-MSMS, and then pharmacokinetic parameters were calculated by non-compartmental analysis using Kinetica program. Effective intestinal permeability (Peff) values were also optimized to predict the actual average plasma profile of each drug by Nelder-Mead algorithm of the Parameter Estimation module using SimCYP program. Results: All studied drugs showed salivary excretion with strong correlation coefficients between saliva and plasma concentrations. The optimized Peff ranged 1.44–68.3 × 10−4 cm/s for the drugs under investigation. Saliva/plasma concentrations ratios ranged 0.17–1.5. Inter and intra individual variability of primary pharmacokinetic parameters in saliva matrix was either close to or higher than plasma matrix. This requires larger sample size in saliva studies for some drugs. Conclusion: Our results suggest that there is a potential in BA/BE studies for saliva to be considered as a surrogate for plasma concentration, which goes along with drug regulations. The use of saliva instead of plasma in such studies makes them non-invasive, easy and with a lower clinical burden.http://www.sciencedirect.com/science/article/pii/S1319016416301074SECSSalivaBioequivalencePharmacokinetics
collection DOAJ
language English
format Article
sources DOAJ
author Nasir M. Idkaidek
spellingShingle Nasir M. Idkaidek
Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
Saudi Pharmaceutical Journal
SECS
Saliva
Bioequivalence
Pharmacokinetics
author_facet Nasir M. Idkaidek
author_sort Nasir M. Idkaidek
title Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
title_short Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
title_full Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
title_fullStr Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
title_full_unstemmed Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
title_sort comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans
publisher Elsevier
series Saudi Pharmaceutical Journal
issn 1319-0164
publishDate 2017-07-01
description Aims: To study the pharmacokinetics of selected drugs in plasma and saliva matrixes in healthy human volunteers, and to suggest using non-invasive saliva sampling instead of plasma as a surrogate in bioavailability and bioequivalence (BA/BE) studies. Methods: Four different pilot BA/BE studies were done in 12–18 healthy humans. Saliva and plasma samples were collected for 3–5 half life values of metformin, tolterodine, rosuvastatin, and paracetamol after oral dosing. Saliva and plasma samples were assayed using LC-MSMS, and then pharmacokinetic parameters were calculated by non-compartmental analysis using Kinetica program. Effective intestinal permeability (Peff) values were also optimized to predict the actual average plasma profile of each drug by Nelder-Mead algorithm of the Parameter Estimation module using SimCYP program. Results: All studied drugs showed salivary excretion with strong correlation coefficients between saliva and plasma concentrations. The optimized Peff ranged 1.44–68.3 × 10−4 cm/s for the drugs under investigation. Saliva/plasma concentrations ratios ranged 0.17–1.5. Inter and intra individual variability of primary pharmacokinetic parameters in saliva matrix was either close to or higher than plasma matrix. This requires larger sample size in saliva studies for some drugs. Conclusion: Our results suggest that there is a potential in BA/BE studies for saliva to be considered as a surrogate for plasma concentration, which goes along with drug regulations. The use of saliva instead of plasma in such studies makes them non-invasive, easy and with a lower clinical burden.
topic SECS
Saliva
Bioequivalence
Pharmacokinetics
url http://www.sciencedirect.com/science/article/pii/S1319016416301074
work_keys_str_mv AT nasirmidkaidek comparativeassessmentofsalivaandplasmafordrugbioavailabilityandbioequivalencestudiesinhumans
_version_ 1725466545578049536