Detection of Paracetamol as substrate of the gut microbiome

Imran Mukhtar; Haseeb Anwar; Ghulam Hussain; Azhar Rasul; Syed Ali Raza Naqvi; Muhammad Naeem Faisal; Imtiaz Mustafa; Saima Malik; Arslan Shaukat; Osman Asghar Mirza; Muhammad Umar Sohail

Detection of Paracetamol as substrate of the gut microbiome

Imran Mukhtar, Haseeb Anwar, Ghulam Hussain, Azhar Rasul, Syed Ali Raza Naqvi, Muhammad Naeem Faisal, Imtiaz Mustafa, Saima Malik, Arslan Shaukat, Osman Asghar Mirza, Muhammad Umar Sohail

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Abstract

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

Original language	English
Journal	Pakistan Journal of Pharmaceutical Sciences
Volume	32
Issue number	2 (Supplementary)
Pages (from-to)	751-757
Number of pages	7
ISSN	1011-601X
Publication status	Published - Mar 2019

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@article{b484a089124348b88b5779b7483481b5,

title = "Detection of Paracetamol as substrate of the gut microbiome",

abstract = "Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.",

author = "Imran Mukhtar and Haseeb Anwar and Ghulam Hussain and Azhar Rasul and Naqvi, {Syed Ali Raza} and Faisal, {Muhammad Naeem} and Imtiaz Mustafa and Saima Malik and Arslan Shaukat and Mirza, {Osman Asghar} and Sohail, {Muhammad Umar}",

year = "2019",

month = mar,

language = "English",

volume = "32",

pages = "751--757",

journal = "Pakistan Journal of Pharmaceutical Sciences",

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TY - JOUR

T1 - Detection of Paracetamol as substrate of the gut microbiome

AU - Mukhtar, Imran

AU - Anwar, Haseeb

AU - Hussain, Ghulam

AU - Rasul, Azhar

AU - Naqvi, Syed Ali Raza

AU - Faisal, Muhammad Naeem

AU - Mustafa, Imtiaz

AU - Malik, Saima

AU - Shaukat, Arslan

AU - Mirza, Osman Asghar

AU - Sohail, Muhammad Umar

PY - 2019/3

Y1 - 2019/3

N2 - Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

AB - Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

M3 - Journal article

C2 - 31103967

SN - 1011-601X

VL - 32

SP - 751

EP - 757

JO - Pakistan Journal of Pharmaceutical Sciences

JF - Pakistan Journal of Pharmaceutical Sciences

IS - 2 (Supplementary)

ER -

Detection of Paracetamol as substrate of the gut microbiome

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