Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Pharmaceuticals, Volume 12, Issue 3 (September 2019)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-12
Export citation of selected articles as:
Open AccessEditorial
Special Issue “Targets, Tracers and Translation Novel Radiopharmaceuticals Boost Nuclear Medicine”
Pharmaceuticals 2019, 12(3), 111; https://doi.org/10.3390/ph12030111
Received: 15 July 2019 / Accepted: 15 July 2019 / Published: 18 July 2019
Viewed by 146 | PDF Full-text (146 KB) | HTML Full-text | XML Full-text
Abstract
This is the fourth Special Issue in Pharmaceuticals within the last six years dealing with aspects of radiopharmaceutical sciences [...] Full article
Open AccessArticle
Safety Pharmacological Evaluation of the Coffee Component, Caffeoylquinic Acid, and Its Metabolites, Using Ex Vivo and In Vitro Profiling Assays
Pharmaceuticals 2019, 12(3), 110; https://doi.org/10.3390/ph12030110
Received: 6 June 2019 / Revised: 8 July 2019 / Accepted: 9 July 2019 / Published: 17 July 2019
Viewed by 148 | PDF Full-text (1620 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Although coffee components have gained interest for use as pharmaceuticals, little is known about their safety pharmacological effects. Hence, we aimed to evaluate the safety pharmacological effects of a chlorogenic acid (CGA)-related compound contained in coffee, 5-O-caffeoylquinic acid (5-CQA), and its [...] Read more.
Although coffee components have gained interest for use as pharmaceuticals, little is known about their safety pharmacological effects. Hence, we aimed to evaluate the safety pharmacological effects of a chlorogenic acid (CGA)-related compound contained in coffee, 5-O-caffeoylquinic acid (5-CQA), and its metabolites, 5-O-feruloylquinic acid (5-FQA), caffeic acid (CA), and ferulic acid (FA). Langendorff perfused heart assay, electrophysiological assay of acute rat hippocampal slices, and in vitro Magnus assay of gastrointestinal tracts were conducted at 1–100 µM. Moreover, in vitro profiling assays against 38 major targets were conducted. In the Langendorff assay, no significant adverse effects were observed. In the electrophysiological assay, although epileptiform discharge rates were increased at 10 µM CA with 4-aminopyridine, and area under the curve (AUC) and number of population spike were increased at 10 µM FA with bicuculline, dose dependency was not confirmed, and no significant changes were observed at 1 µM and by CGAs alone. In the Magnus assay, a slight increase in contraction activity was observed at >1 µM FA in the stomach fundi and 100 µM 5-CQA in the ileum, suggesting enterokinesis promotion. No significant interactions were observed in the in vitro profiling assays. Therefore, CGAs could have a fundamental function as safe pharmaceuticals. Full article
Figures

Figure 1

Open AccessArticle
Fenofibrate Nanocrystal Composite Microparticles for Intestine-Specific Oral Drug Delivery System
Pharmaceuticals 2019, 12(3), 109; https://doi.org/10.3390/ph12030109
Received: 16 June 2019 / Revised: 9 July 2019 / Accepted: 10 July 2019 / Published: 16 July 2019
Viewed by 158 | PDF Full-text (13982 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Hydrophobic drug nanocrystals (NCs) manufactured by particle engineering have been extensively investigated for enhanced oral bioavailability and therapeutic effectiveness. However, there are significant drawbacks, including fast dissolution of the nanocrystals in the gastric environment, leading to physicochemical instability. To solves this issue, we [...] Read more.
Hydrophobic drug nanocrystals (NCs) manufactured by particle engineering have been extensively investigated for enhanced oral bioavailability and therapeutic effectiveness. However, there are significant drawbacks, including fast dissolution of the nanocrystals in the gastric environment, leading to physicochemical instability. To solves this issue, we developed an innovative technique that involves the encapsulation of nanocrystals in composite spherical microparticles (NCSMs). Fenofibrate (FNB) NCs (FNB-NCs) manufactured by a wet stirred media milling (WSMM) technique and an ionotropic crosslinking method were used for FNB-NC encapsulation within gastroresistant NCSMs. Various solid-state methods were used for characterizing NCSMs. The pH-sensitive NCSMs showed a site-specific release pattern at alkaline pH and nearly 0% release at low pH (gastric environment). This phenomenon was confirmed by a real-time in situ UV-imaging system known as the surface dissolution imager (SDI), which was used to monitor drug release events by measuring the color intensity and concentration gradient formation. All these results proved that our NCSM approach is an innovative idea in oral drug delivery systems, as it resolves significant challenges in the intestine-specific release of hydrophobic drugs while avoiding fast dissolution or burst release. Full article
Figures

Figure 1

Open AccessArticle
Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities
Pharmaceuticals 2019, 12(3), 108; https://doi.org/10.3390/ph12030108
Received: 15 June 2019 / Revised: 8 July 2019 / Accepted: 10 July 2019 / Published: 12 July 2019
Viewed by 223 | PDF Full-text (3677 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses [...] Read more.
N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM). On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM). Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a). Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
Figures

Graphical abstract

Open AccessArticle
Long Term Effectiveness of Photodynamic Therapy for CIN Treatment
Pharmaceuticals 2019, 12(3), 107; https://doi.org/10.3390/ph12030107
Received: 16 May 2019 / Revised: 21 June 2019 / Accepted: 29 June 2019 / Published: 12 July 2019
Viewed by 177 | PDF Full-text (4461 KB) | HTML Full-text | XML Full-text
Abstract
(1) Background: Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, followed by South-Central Asia and South America. According to the Brazilian National Institute of [...] Read more.
(1) Background: Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, followed by South-Central Asia and South America. According to the Brazilian National Institute of Cancer (INCA), 16,370 new cases of cervical cancer were estimated for each year of the biennium of 2018–2019. About 90% of cervical cancers originate from the malignant progression of cervical intraepithelial neoplasia (CIN) which is classified based on cytohistological characteristics (low- and high-grade lesions). The present study reports the long-term effectiveness of topical photodynamic therapy (PDT) for CIN grades 1 and 2/3 with up to two years of follow up. (2) Methods: A total of 56 patients with CIN 1, ten with CIN 2, and 14 patients for the placebo group were enrolled in this study. (3) Results: 75% (n = 42) of CIN 1 patients presented a complete response to PDT and only 23.2% (n = 13) of recurrence, progression, and/or lesions remaining two years after PDT. For CIN 2/3 patients, 90% were observed to be cured after one and two years of follow up. (4) Conclusions: PDT presented best results two years after a non-invasive, fast, and low-cost procedure and in comparison with the placebo group, preventing the progression of cervical intraepithelial neoplasia and preserving the cervix. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
Figures

Figure 1

Open AccessArticle
Anxiolytic and Antidepressant Effects of the Hydroethanolic Extract from the Leaves of Aloysia polystachya (Griseb.) Moldenke: A Study on Zebrafish (Danio rerio)
Pharmaceuticals 2019, 12(3), 106; https://doi.org/10.3390/ph12030106
Received: 20 May 2019 / Revised: 28 June 2019 / Accepted: 1 July 2019 / Published: 11 July 2019
Viewed by 173 | PDF Full-text (4011 KB) | HTML Full-text | XML Full-text
Abstract
Medicinal plants such as Aloysia polystachya are often used in the treatment of psychiatric diseases, including anxiety- and depression-related humor disturbances. In folk medicine, A. polystachya is used to treat digestive and respiratory tract disturbances, as a sedative and antidepressant agent, and as [...] Read more.
Medicinal plants such as Aloysia polystachya are often used in the treatment of psychiatric diseases, including anxiety- and depression-related humor disturbances. In folk medicine, A. polystachya is used to treat digestive and respiratory tract disturbances, as a sedative and antidepressant agent, and as a tonic for the nerves. This study aimed to evaluate the antidepressant and anxiolytic effect from the hydroethanolic extract from the leaves of Aloysia polystachya (HELAp) in zebrafish. The extract was analyzed through ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS) and the main compound detected was acteoside. HELAp was administered orally (10 mg/kg) and through immersion (mg/L). The anxiolytic activity was evaluated through the scototaxis (light–dark) test using caffeine as an anxiogenic agent and buspirone as a positive control. The parameters assessed were: period spent in the white compartment (s), latency (s), alternations (n), erratic swims (n), period of freezing (s), thigmotaxis (s), and risk evaluation (n). The antidepressant effect was evaluated through the novel tank diving test using 1% ethanol, unpredictable chronic stress, and social isolation as depressors; fluoxetine was used as a positive control. The parameters assessed were: period spent at the top of the tank, latency, quadrants crossed, erratic swim, period of freezing, and distance of swam. The main chemical compound of HELAp was acteoside. The administration of the extract on zebrafish managed to revert the anxiogenic effect of caffeine without impairing their locomotion. Additionally, the treatment exerted antidepressant activity similarly to fluoxetine. Overall, the results suggest a significant anxiolytic and antidepressant activity to the extract, which is probably due to the presence of the major compound, acteoside. Full article
Figures

Graphical abstract

Open AccessArticle
Synthesis of Saponite Based Nanocomposites to Improve the Controlled Oral Drug Release of Model Drug Quinine Hydrochloride Dihydrate
Pharmaceuticals 2019, 12(3), 105; https://doi.org/10.3390/ph12030105
Received: 16 April 2019 / Revised: 18 June 2019 / Accepted: 24 June 2019 / Published: 10 July 2019
Viewed by 192 | PDF Full-text (3712 KB) | HTML Full-text | XML Full-text
Abstract
In the present research study, a 2:1 type of smectite clay minerals, namely natural saponite (NSAP) and synthetic saponite (SSAP), was demonstrated for the first time to be controlled drug release host materials for the model drug quinine hydrochloride dihydrate (QU). The popular [...] Read more.
In the present research study, a 2:1 type of smectite clay minerals, namely natural saponite (NSAP) and synthetic saponite (SSAP), was demonstrated for the first time to be controlled drug release host materials for the model drug quinine hydrochloride dihydrate (QU). The popular sol–gel hydrothermal technique was followed for the synthesis of saponite. The QU was ion exchanged and intercalated into an interlayered gallery of synthetic as well as natural saponite matrices. The developed QU-loaded hybrid composite materials along with the pristine materials were characterized by powder X-ray diffraction (PXRD), Fourier transformed infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), the Brunauer–Emmett–Teller method (BET) for surface area (SA), and scanning electron microscopy (SEM). The characterization of material results using DSC, FTIR and PXRD confirmed the presence of saponite clay mineral phases in the original and the synthesized saponite samples. Similarly, the drug-loaded composites confirmed the successful intercalation of QU drug on the natural and synthesized saponite matrices. The oral drug release performance of both nanocomposites along with pure quinine drug was monitored in sequential buffer environments at 37 ± 0.5 °C. These composite hybrid materials showed the superior controlled release of QU in gastric fluid (pH = 1.2) and intestinal fluid (pH = 7.4). QU release was best fitted in the Korsmeyer–Peppas kinetic model and demonstrated a diffusion-controlled release from nanocomposite layered materials. The observed controlled drug release results suggest that the applied natural/synthetic saponite matrices have the potential to provide critical design parameters for the development of bioengineered materials for controlled drug release. Full article
Figures

Figure 1

Open AccessArticle
The Cannabinoid-Like Compound, VSN16R, Acts on Large Conductance, Ca2+-Activated K+ Channels to Modulate Hippocampal CA1 Pyramidal Neuron Firing
Pharmaceuticals 2019, 12(3), 104; https://doi.org/10.3390/ph12030104
Received: 24 May 2019 / Revised: 17 June 2019 / Accepted: 20 June 2019 / Published: 4 July 2019
Viewed by 267 | PDF Full-text (1319 KB) | HTML Full-text | XML Full-text
Abstract
Large conductance, Ca2+-activated K+ (BKCa) channels are widely expressed in the central nervous system, where they regulate action potential duration, firing frequency and consequential neurotransmitter release. Moreover, drug action on, mutations to, or changes in expression levels of [...] Read more.
Large conductance, Ca2+-activated K+ (BKCa) channels are widely expressed in the central nervous system, where they regulate action potential duration, firing frequency and consequential neurotransmitter release. Moreover, drug action on, mutations to, or changes in expression levels of BKCa can modulate neuronal hyperexcitability. Amongst other potential mechanisms of action, cannabinoid compounds have recently been reported to activate BKCa channels. Here, we examined the effects of the cannabinoid-like compound (R,Z)-3-(6-(dimethylamino)-6-oxohex-1-en-1-yl)-N-(1-hydroxypropan-2-yl) benzamide (VSN16R) at CA1 pyramidal neurons in hippocampal ex vivo brain slices using current clamp electrophysiology. We also investigated effects of the BKCa channel blockers iberiotoxin (IBTX) and the novel 7-pra-martentoxin (7-Pra-MarTx) on VSN16R action. VSN16R (100 μM) increased first and second fast after-hyperpolarization (fAHP) amplitude, decreased first and second inter spike interval (ISI) and shortened first action potential (AP) width under high frequency stimulation protocols in mouse hippocampal pyramidal neurons. IBTX (100 nM) decreased first fAHP amplitude, increased second ISI and broadened first and second AP width under high frequency stimulation protocols; IBTX also broadened first and second AP width under low frequency stimulation protocols. IBTX blocked effects of VSN16R on fAHP amplitude and ISI. 7-Pra-MarTx (100 nM) had no significant effects on fAHP amplitude and ISI but, unlike IBTX, shortened first and second AP width under high frequency stimulation protocols; 7-Pra-MarTx also shortened second AP width under low frequency stimulation protocols. However, in the presence of 7-Pra-MarTx, VSN16R retained some effects on AP waveform under high frequency stimulation protocols; moreover, VSN16R effects were revealed under low frequency stimulation protocols. These findings demonstrate that VSN16R has effects in native hippocampal neurons consistent with its causing an increase in initial firing frequency via activation of IBTX-sensitive BKCa channels. The differential pharmacological effects described suggest that VSN16R may differentially target BKCa channel subtypes. Full article
(This article belongs to the Special Issue Cannabinoids as Medicines)
Figures

Figure 1

Open AccessArticle
Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives
Pharmaceuticals 2019, 12(3), 103; https://doi.org/10.3390/ph12030103
Received: 15 May 2019 / Revised: 25 June 2019 / Accepted: 27 June 2019 / Published: 2 July 2019
Viewed by 306 | PDF Full-text (2687 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5′ and 6′-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer’s disease therapy. Continuing with our research on this topic, we [...] Read more.
Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5′ and 6′-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer’s disease therapy. Continuing with our research on this topic, we report herein on the synthesis and biological evaluation of a variety of novel terminal isonucleosides and theobromine isonucleotide analogs. Xylofuranose-based purine or uracil 5′-isonucleosides and xylofuranos-5′-yl or glucos-6′-yl theobromine derivatives were accessed via Mitsunobu coupling between partially protected xylofuranose or glucofuranose derivatives with a nucleobase using conventional or microwave-assisted heating conditions. Theobromine-containing N-isonucleosidyl sulfonamide and phosphoramidate derivatives were synthesized from isonucleosidyl acetate precursors. The most active compounds in the cholinesterase inhibition assays were a glucopyranose-based theobromine isonucleosidyl acetate, acting as a dual inhibitor of acetylcholinesterase (AChE, Ki = 3.1 µM) and butyrylcholinesterase (BChE, Ki = 5.4 µM), and a 2-O,4-O-bis-xylofuranos-5′-yl uracil derivative, which displayed moderate inhibition of AChE (Ki = 17.5 µM). Docking studies revealed that the active molecules are positioned at the gorge entrance and at the active site of AChE. None of the compounds revealed cytoxic activity to cancer cells as well as to non-malignant mouse fibroblasts. Full article
(This article belongs to the Special Issue Carbohydrates 2018)
Figures

Graphical abstract

Open AccessCommunication
α-Glucosidase Inhibitory Activity of Cycloartane-Type Triterpenes Isolated from Indonesian Stingless Bee Propolis and Their Structure–Activity Relationship
Pharmaceuticals 2019, 12(3), 102; https://doi.org/10.3390/ph12030102
Received: 10 May 2019 / Revised: 21 June 2019 / Accepted: 26 June 2019 / Published: 1 July 2019
Viewed by 327 | PDF Full-text (1981 KB) | HTML Full-text | XML Full-text
Abstract
This study reports on the antioxidant activity and α-glucosidase inhibitory activity of five cycloartane-type triterpenes isolated from Indonesian stingless bee (Tetragonula sapiens Cockerell) propolis and their structure–activity relationships. The structure of the triterpenes was determined to include mangiferolic acid (1), [...] Read more.
This study reports on the antioxidant activity and α-glucosidase inhibitory activity of five cycloartane-type triterpenes isolated from Indonesian stingless bee (Tetragonula sapiens Cockerell) propolis and their structure–activity relationships. The structure of the triterpenes was determined to include mangiferolic acid (1), Cycloartenol (2), ambonic acid (3), mangiferonic acid (4), and ambolic acid (5). The inhibitory test results of all isolated triterpenes against α-glucosidase showed a high potential for inhibitory activity with an IC50 range between 2.46 and 10.72 µM. Among the compounds tested, mangiferonic acid (4) was the strongest α-glucosidase inhibitor with IC50 2.46 µM compared to the standard (–)-epicatechin (1991.1 µM), and also had antioxidant activities with IC50 values of 37.74 ± 6.55 µM. The study on the structure–activity relationships among the compounds showed that the ketone group at C-3 and the double bonds at C-24 and C-25 are needed to increase the α-glucosidase inhibitory activity. The carboxylic group at C-26 is also more important for increasing the inhibitory activity compared with the methyl group. This study provides an approach to help consider the structural requirements of cycloartane-type triterpenes from propolis as α-glucosidase inhibitors. An understanding of these requirements is deemed necessary to find a new type of α-glucosidase inhibitor from the cycloartane-type triterpenes or to improve those inhibitors that are known to help in the treatment of diabetes. Full article
(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs)
Figures

Figure 1

Open AccessReview
Antiviral Agents in Development for Zika Virus Infections
Pharmaceuticals 2019, 12(3), 101; https://doi.org/10.3390/ph12030101
Received: 31 May 2019 / Revised: 25 June 2019 / Accepted: 26 June 2019 / Published: 29 June 2019
Viewed by 460 | PDF Full-text (888 KB) | HTML Full-text | XML Full-text
Abstract
In 1947, Zika virus (ZIKV), a mosquito-borne flavivirus was identified in Uganda and subsequently spread to Asia and the Pacific regions. In 2015, it was introduced in Brazil causing an important social and sanitary alarm due to its increased virulence and rapid dissemination. [...] Read more.
In 1947, Zika virus (ZIKV), a mosquito-borne flavivirus was identified in Uganda and subsequently spread to Asia and the Pacific regions. In 2015, it was introduced in Brazil causing an important social and sanitary alarm due to its increased virulence and rapid dissemination. Importantly, ZIKV infections have been associated with severe neurological complications such as Guillain–Barré syndrome and microcephaly in fetuses and newborns. Although enormous efforts were made by investigators in the development of effective countermeasures against ZIKV, there is still no approved specific antiviral drug for the treatment of ZIKV infections. Herein, we review several anti ZIKV candidates including drugs targeting both the virus (structural proteins and enzymes) and cellular elements. Full article
(This article belongs to the Special Issue Zika Virus: Therapeutic Advances)
Figures

Figure 1

Open AccessArticle
Changes in Iron Metabolism Induced by Anti-Interleukin-6 Receptor Monoclonal Antibody are Associated with an Increased Risk of Infection
Pharmaceuticals 2019, 12(3), 100; https://doi.org/10.3390/ph12030100
Received: 1 June 2019 / Revised: 20 June 2019 / Accepted: 25 June 2019 / Published: 28 June 2019
Viewed by 338 | PDF Full-text (3309 KB) | HTML Full-text | XML Full-text
Abstract
(1) Background: Treatment of patients with rheumatoid arthritis (RA) with an anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (tocilizumab) has been found to influence iron metabolism. The objective of the present study was to ascertain whether changes in iron metabolism induced by anti-IL-6R biologic therapy [...] Read more.
(1) Background: Treatment of patients with rheumatoid arthritis (RA) with an anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (tocilizumab) has been found to influence iron metabolism. The objective of the present study was to ascertain whether changes in iron metabolism induced by anti-IL-6R biologic therapy were independently associated with an increased infection risk. (2) Methods: A prospective longitudinal study of patients with RA treated with tocilizumab was conducted. RA patients treated with an antitumor necrosis factor α monoclonal antibody were also included as a control group. The primary outcome was occurrence of infection during the first 24 months of biologic therapy. (3) Results: A total of 15 patients were included, with a mean age of 51.0 ± 4,1 and 73.3% (n = 11) female. A multivariate survival regression model, adjusted for confounding factors, was fitted for each of the iron metabolism variables. Hazard ratios for being above the median of each parameter was considered. Transferrin saturation above the median value (>32.1%) was associated with a higher infection risk (HR 4.3; 95%CI 1.0–19.69; p = 0.05). Similarly, although non-significantly, higher serum iron was strongly associated with infection occurrence. (4) Conclusions: This study identified a probable association between infection risk and higher serum iron and transferrin saturation in patients with RA on anti-IL-6R biologic therapy. We suggest that both these parameters should be considered relevant contributing factors for infection occurrence in patients on anti-IL-6R therapy. Full article
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
Figures

Figure 1

Pharmaceuticals EISSN 1424-8247 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top