Ibuprofen : clinical pharmacology, medical uses and adverse effects

418 Pages·2015·10.31 MB·English

PHARMACOLOGY - RESEARCH, SAFETY TESTING AND REGULATION

I
BUPROFEN

C P , M
LINICAL HARMACOLOGY EDICAL
USES AND ADVERSE EFFECTS

No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or
by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no
expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No
liability is assumed for incidental or consequential damages in connection with or arising out of information
contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in
rendering legal, medical or any other professional services.
P - R , S
HARMACOLOGY ESEARCH AFETY
T R
ESTING AND EGULATION

Additional books in this series can be found on Nova’s website
under the Series tab.

Additional e-books in this series can be found on Nova’s website
under the e-book tab.
PHARMACOLOGY - RESEARCH, SAFETY TESTING AND REGULATION

I
BUPROFEN

C P , M
LINICAL HARMACOLOGY EDICAL
USES AND ADVERSE EFFECTS

WILTON C. CARTER
AND
BRANT R. BROWN
EDITORS

New York
Copyright © 2013 by Nova Science Publishers, Inc.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system or
transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical
photocopying, recording or otherwise without the written permission of the Publisher.

For permission to use material from this book please contact us:
Telephone [phone]; Fax [phone]
Web Site: http://www.novapublishers.com

NOTICE TO THE READER
The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or
implied warranty of any kind and assumes no responsibility for any errors or omissions. No
liability is assumed for incidental or consequential damages in connection with or arising out of
information contained in this book. The Publisher shall not be liable for any special,
consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or
reliance upon, this material. Any parts of this book based on government reports are so indicated
and copyright is claimed for those parts to the extent applicable to compilations of such works.

Independent verification should be sought for any data, advice or recommendations contained in
this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage
to persons or property arising from any methods, products, instructions, ideas or otherwise
contained in this publication.

This publication is designed to provide accurate and authoritative information with regard to the
subject matter covered herein. It is sold with the clear understanding that the Publisher is not
engaged in rendering legal or any other professional services. If legal or any other expert
assistance is required, the services of a competent person should be sought. FROM A
DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE
AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS.

Additional color graphics may be available in the e-book version of this book.

Library of Congress Cataloging-in-Publication Data

Library of Congress Control Number: 2013935914
ISBN: (cid:28)(cid:26)(cid:27)(cid:16)(cid:20)(cid:16)(cid:25)(cid:21)(cid:25)(cid:20)(cid:27)(cid:16)(cid:25)(cid:25)(cid:19)(cid:16)(cid:25) (eBook)

Published by Nova Science Publishers, Inc. † New York
Contents

Preface vii
Chapter 1 Ibuprofen in the Aquatic Environment: Occurrence, Ecotoxicity
and Water Remediation Technologies 1
Ana P. Carvalho, Ana S. Mestre,
Marta Andrade and Conchi O. Ania
Chapter 2 Ecological Risk Assessment of Ibuprofen in
Aquatic Environments: An Approach for Complex
Mixture of Contaminants 85
Karina Boltes and Víctor González-Naranjo
Chapter 3 Advanced Oxidation Processes for Ibuprofen Removal
and Ecotoxicological Risk Assessment
of Degradation Intermediates 159
Krisztina Gajda-Schrantz, Eszter Arany,
Erzsébet Illés, Emese Szabó, Zsolt Pap,
Erzsébet Takács and László Wojnárovits
Chapter 4 Ibuprofen: Associated Adverse Drug Reactions 233
Radu M. Nanau and Manuela G. Neuman
Chapter 5 Hybrid Multifunctional Ibuprofen Drugs:
New Generation and Novel Possibilities 275
V. V. Bezuglov, M. G. Akimov and I. V. Serkov
Chapter 6 Ibuprofen Delivery: Pharmaceutical Nanotechnology Approach 311
Ljiljana Djekic
Chapter 7 Vibrational Dynamics and Chiral Properties of Racemate
and Pure Enantiomers of Ibuprofen Complexed
in Cyclodextrins: State of Art 349
V. Crupi, G. Guella, D. Majolino, I. Mancini,
B. Rossi, V. Venuti and P. Verrocchio
vi Contents
Chapter 8 Therapeutic Effects of Ibuprofen on Transgenic Mice
Models of Neurodegenerative Diseases 369
Kazunari Sekiyama, Masayo Fujita, Akio Sekigawa,
Yoshiki Takamatsu and Makoto Hashimoto
Chapter 9 The Use of Ibuprofen for Pain Relief in Gynecology: A Review 377
Sarit Avraham and Daniel S. Seidman
Index 385
Preface

In this book, the authors present topical research in the study of the clinical
pharmacology, medical uses, and adverse effects of ibuprofen. Topics discussed include the
occurrence, ecotoxicity and water remediation technologies of ibuprofen in the aquatic
environment; associated adverse drug reaction in ibuprofen use; hybrid multifunctional
ibuprofen drugs; a pharmaceutical nanotechnology approach to ibuprofen delivery;
vibrational dynamics and chiral properties of racemate and pure enantiomers of ibuprofen
complexed in cyclodextrins; therapeutic effects of ibuprofen on transgenic mice models of
neurodegenerative diseases; and the use of ibuprofen for pain relief in gynecology.
Chapter 1 – For the last few decades, emerging pollutants are the object of increasing
public concern among scientists and society. These compounds, also known as contaminants
of emerging concern, are chemicals that originate from industrial, agricultural and human
activities, very often as consumer products and by-products used every day. Examples of this
new class of pollutants include pesticides, solvents, flame retardants, nanoparticles, and
pharmaceuticals (prescription and non-prescription human and veterinary compounds) and
personal care products (PPCPs). A common characteristic to all of them is that they are not
included in routine monitoring programs at a worldwide level, but have been added to the
Candidates Contaminant List for prioritizing their regulation in the near future due to their
occurrence, potential health effects, and ecotoxicity.
Ibuprofen is among the most frequently reported active pharmaceutical ingredients in
ambient monitoring studies worldwide, and the second most consistently detected one in
finished drinking water at high concentrations (> 1 ppb). This is due to the large consumption
of this popular analgesic allied with the poor efficiency of conventional water treatment
processes for its complete removal/degradation. Even though the amount of ibuprofen
allowed in different sorts of water is not regulated at the moment, many efforts from the
scientific community are currently being directed on its monitoring, removal and/or
degradation. In fact, water is an essential resource for life in all ecosystems and so far little is
known about the occurrence, fate, synergistic and long-term effects of active pharmaceutical
ingredients and their metabolites following their end-use.
This chapter aims to provide the current state of scientific knowledge regarding ibuprofen
occurrence, fate and toxicological effects in water environments and aquatic organisms, as
well as remediation technologies. The fate of ibuprofen during conventional water treatments
is presented along with a review of recent advances of water treatment methodologies to
control the occurrence of pharmaceuticals in water environments, focusing in their
viii Wilton C. Carter and Brant R. Brown
performance for ibuprofen mitigation. Besides reviewing the performance of treatment
methodologies individually, hybrid processes, combining membrane filtration with
biodegradation, adsorption and/or advanced oxidation processes, will be also addressed. Such
hybrid technologies can effectively remove a large variety of micropollutants, which respond
distinctively to each individual treatment process, and so rise as the key towards an effective
water treatment system that allows to obtain effluents with high quality standards.
Chapter 2 – Recently, it has been shown that conventional wastewater treatment plants
(WWTP) cannot completely remove many organic micropollutants. The pharmaceuticals and
personal Care Products, PPCPs, are extensively found in water environmental samples. In this
group, ibuprofen and triclosan are very representative due to their persistency and ubiquity.
Ibuprofen is a non-steroidal anti-inflammatory, analgesic, and antipyretic drug. It is an
important non-prescription drug widely used. And triclosan, an antimicrobial chemical, is
considered as persistent pollutant in the environment. Industrial chemicals and pesticide are
also found in waters. The perfluorooctanoic acid, PFOA, very used in industry because of its
chemical and thermal stability, and atrazine, an organochlorine herbicide, is extensively used
in agriculture, and is included in lists of priority pollutants. The occurrence of any emerging
contaminant, even at low concentrations, can lead to chronic health effects especially at
highly contaminated sites, particularly when possible different effects of organic compounds
mixtures could take place. Risk assessment of pharmaceuticals in environment needs
toxicological information from different trophic levels, especially on non-target organisms.
But the studies are usually focused on the evaluation of the effect of a single drug on each
organism used. The studies about combined toxicity are very important because the organic
pollutants residues found in environmental samples usually occur as mixtures, not as single
contaminants and the ecotoxicity values obtained for individual substances do not provide a
safe rule for mixtures.
Original results of toxicological effects have been obtained for binary, ternary and
quaternary mixtures (including ibuprofen) on green algae. The CI-isobologram equation was
applied to obtain real toxicity data taking in account the type and level of interactions
between pollutants studied. These parameters were used to carry out the risk assessment for
aquatic environment due to the occurrence of ibuprofen solely and combined with other
contaminants.
Chapter 3 – Nowadays huge amounts of pharmaceuticals, among them ibuprofen (IBU),
are consumed worldwide. After administration approximately 40% of the medicine and its
metabolites are excreted. Moreover, in spite of the broad campaigns about the proper disposal
of the unused or expired drugs, uncontrolled quantities land every day in the wastewater. Due
to their low biodegradability the wastewater treatment plants (WWTPs) are not able to
remove them completely from the effluent; therefore they are present in the environment in
their initial form and as their metabolites (1-hydroxy-ibuprofen (1-OH-IBU), 2-hydroxy-
ibuprofen (2-OH-IBU), 3-hydroxy-ibuprofen (3-OH-IBU), carboxy-ibuprofen (CA-IBU) and
carboxy-hydratropic acid (CA-HA). Several studies investigate the occurrence of these
compounds and IBU itself in WWTP influents and effluents, drinking and natural waters. The
detected values are mainly in the 10–12 – 10–9 mol dm–3 range.
Advanced Oxidation Processes (AOPs) are effective methods to oxidize and mineralize
IBU by using non-selective and highly reactive (mainly hydroxyl, OH) radicals, which can
be generated by vacuum-ultraviolet (VUV) irradiation, high-energy ionizing radiation,
photocatalysis, Fenton reaction, through the degradation of hydrogen peroxide or ozone. The