Pharmaceuticals

Research

20 pages, 1476 KiB

Open AccessArticle

Application of Thin-Layer Chromatography in Combination with Densitometry for the Determination of Diclofenac in Enteric Coated Tablets

by Wioletta Parys, Alina Pyka-Pająk and Małgorzata Dołowy

Pharmaceuticals 2019, 12(4), 183; https://doi.org/10.3390/ph12040183 - 16 Dec 2019

Cited by 11 | Viewed by 7397

Abstract

Diclofenac belongs to the drug class non-steroidal anti-inflammatory drugs widely used in Europe as well as all over the world. Thus, it is important to conduct research on its quality control of available pharmaceutical preparations like for example enteric coated tablets. Among various [...] Read more.

Diclofenac belongs to the drug class non-steroidal anti-inflammatory drugs widely used in Europe as well as all over the world. Thus, it is important to conduct research on its quality control of available pharmaceutical preparations like for example enteric coated tablets. Among various analytical techniques, thin-layer chromatography (TLC) is ideal for this task due to their short time analysis, ease of operation and low cost. Hence, the aim of this study was to develop the optimal conditions of analysis and quantitative determination of diclofenac sodium in enteric tablets by using TLC in combination with densitometry. Of all chromatographic systems tested, the best is the one which consists of silica gel 60F₂₅₄ and cyclohexane: chloroform:methanol:glacial acetic acid (6:3:0.5:0.5 v/v) as the mobile phase, which allows the successful separation of examined diclofenac sodium as active component and the largest number (twelve) of its degradation products as potential impurities of its pharmaceutical products. This indicates that the newly developed method is more effective than previously reported assays by Starek and Krzek. Linearity range was found to be 4.00–18.00 μg/spot for diclofenac sodium. The results of the assay of enteric tablet formulations equals 98.8% of diclofenac sodium in relation to label claim is in a good agreement with pharmaceutical requirements. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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14 pages, 5671 KiB

Open AccessArticle

Metabolism and Pharmacokinetic Study of the Boron-Containing Prodrug of Belinostat (ZL277), a Pan HDAC Inhibitor with Enhanced Bioavailability

by Changde Zhang, Shanchun Guo, Qiu Zhong, Qiang Zhang, Ahamed Hossain, Shilong Zheng and Guangdi Wang

Pharmaceuticals 2019, 12(4), 180; https://doi.org/10.3390/ph12040180 - 8 Dec 2019

Cited by 10 | Viewed by 4290

Abstract

ZL277 is a prodrug of belinostat with enhanced bioavailability and efficacy as a pan histone deacetylase (HDAC) inhibitor. In this study, we investigated the metabolism and pharmacokinetics of ZL277 in liver S9 fractions, liver microsomes, liver cytosol, and in mice. Metabolic products were [...] Read more.

ZL277 is a prodrug of belinostat with enhanced bioavailability and efficacy as a pan histone deacetylase (HDAC) inhibitor. In this study, we investigated the metabolism and pharmacokinetics of ZL277 in liver S9 fractions, liver microsomes, liver cytosol, and in mice. Metabolic products were identified and quantified by a combination of liquid chromatography and tandem mass spectrometry. The in vitro metabolic profile of ZL277 includes ZL277-B(OH)₂-452, the major oxidative metabolite ZL277-OH-424, the active ingredient belinostat, belinostat amide, belinostat acid, and methylated belinostat in liver S9 fractions. Both ZL277-OH-424 and belinostat underwent further glucuronidation in liver microsome, whereas only ZL277-OH-424, but not belinostat, underwent some level of sulfation in rat liver cytosols. These metabolites were examined in plasma and in a breast tumor model in vivo. They were also examined in urine and feces from mice treated with ZL277. The pharmacokinetic study of ZL277 showed the parameters of active drug belinostat with a half-life (t_1/2) of 10.7 h, an area under curve value (AUC) of 1506.9 ng/mL*h, and a maximum plasma concentration (C_max) of 172 ng/mL, reached 3 h after a single dose of 10 mg/kg. The hydrolysis product of the prodrug, ZL277-B(OH)₂-452 showed an AUC of 8306 ng/mL*h and C_max of 931 ng/mL 3 h after drug administration. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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Review

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15 pages, 4056 KiB

Open AccessReview

Chiral Switch: Between Therapeutical Benefit and Marketing Strategy

by Gabriel Hancu and Adriana Modroiu

Pharmaceuticals 2022, 15(2), 240; https://doi.org/10.3390/ph15020240 - 17 Feb 2022

Cited by 67 | Viewed by 14125

Abstract

Chirality of pharmaceutical substances is an important aspect in drug research because it determines how enantiomers will interact with chiral biological targets. Enantiomers of a chiral drug can have different pharmacokinetic and pharmacological profiles; consequently, using a single pure enantiomer instead of a [...] Read more.

Chirality of pharmaceutical substances is an important aspect in drug research because it determines how enantiomers will interact with chiral biological targets. Enantiomers of a chiral drug can have different pharmacokinetic and pharmacological profiles; consequently, using a single pure enantiomer instead of a racemate can enhance the effectiveness and/or safety of the treatment. The tendencies of modern pharmaceutical industry regarding the current market of chiral drugs are divided between the chiral switch of previously used racemates and the development of new enantiopure drugs. The term chiral switch refers to the replacement on the market of a previously approved racemate with its single enantiomer version. The potential advantages of chiral switch can be related to a higher therapeutic index due to better potency, selectivity and fewer adverse effects, faster onset of action and exposure of the patient to lower drug dosages. However, chiral switch is also a strategy that permits manufacturers to keep market exclusivity for chiral pharmaceuticals that have lost their patent protection, even if the pure enantiomers have not demonstrated higher effectiveness or safety profile compared with the racemates. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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17 pages, 2385 KiB

Open AccessReview

2021 FDA TIDES (Peptides and Oligonucleotides) Harvest

by Danah Al Shaer, Othman Al Musaimi, Fernando Albericio and Beatriz G. de la Torre

Pharmaceuticals 2022, 15(2), 222; https://doi.org/10.3390/ph15020222 - 13 Feb 2022

Cited by 54 | Viewed by 7274

Abstract

From the medical, pharmaceutical, and social perspectives, 2021 has been a year dominated by the COVID-19 pandemic. However, despite this global health crisis, the pharmaceutical industry has continued its endeavors, and 2021 could be considered an excellent year in terms of the drugs [...] Read more.

From the medical, pharmaceutical, and social perspectives, 2021 has been a year dominated by the COVID-19 pandemic. However, despite this global health crisis, the pharmaceutical industry has continued its endeavors, and 2021 could be considered an excellent year in terms of the drugs accepted by the US Food and Drug Administration (FDA). Thus, during this year, the FDA has approved 50 novel drugs, of which 36 are new chemical entities and 14 biologics. It has also authorized 10 TIDES (8 peptides, 2 oligonucleotides), in addition to 2 antibody-drug conjugates (ADCs) whose structures contain peptides. Thus, TIDES have accounted for about 24% of the approvals in the various drug categories. Importantly, this percentage has surpassed the figure in 2020 (10%), thus reflecting the remarkable success of TIDES. In this review, the approved TIDE-based drugs are analyzed on the basis of their chemical structure, medical target, mode of action, administration route, and adverse effects. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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11 pages, 1671 KiB

Open AccessEditor’s ChoiceReview

Baloxavir Marboxil: An Original New Drug against Influenza

by François Dufrasne

Pharmaceuticals 2022, 15(1), 28; https://doi.org/10.3390/ph15010028 - 24 Dec 2021

Cited by 26 | Viewed by 6946

Abstract

Baloxavir marboxil is a new drug developed in Japan by Shionogi to treat seasonal flu infection. This cap-dependent endonuclease inhibitor is a prodrug that releases the biologically active baloxavir acid. This new medicine has been marketed in Japan, the USA and Europe. It [...] Read more.

Baloxavir marboxil is a new drug developed in Japan by Shionogi to treat seasonal flu infection. This cap-dependent endonuclease inhibitor is a prodrug that releases the biologically active baloxavir acid. This new medicine has been marketed in Japan, the USA and Europe. It is well tolerated (more than 1% of the patients experienced diarrhea, bronchitis, nausea, nasopharyngitis, and headache), and both influenza A and B viruses are sensitive, although the B strain is more resistant due to variations in the amino acid residues in the binding site. The drug is now in post-marketing pharmacovigilance phase, and its interest will be especially re-evaluated in the future during the annual flu outbreaks. It has been also introduced in a recent clinical trial against COVID-19 with favipiravir. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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43 pages, 2072 KiB

Open AccessReview

Sildenafil 4.0—Integrated Synthetic Chemistry, Formulation and Analytical Strategies Effecting Immense Therapeutic and Societal Impact in the Fourth Industrial Era

by Andreas Ouranidis, Anastasia Tsiaxerli, Elisavet Vardaka, Catherine K. Markopoulou, Constantinos K. Zacharis, Ioannis Nicolaou, Dimitris Hatzichristou, Anna-Bettina Haidich, Nikolaos Kostomitsopoulos and Kyriakos Kachrimanis

Pharmaceuticals 2021, 14(4), 365; https://doi.org/10.3390/ph14040365 - 15 Apr 2021

Cited by 18 | Viewed by 12274

Abstract

Sildenafil is a potent selective, reversible inhibitor of phosphodiesterase type 5 (PDE5) approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. Whilst twenty years have passed since its original approval by the US Food and Drug Administration (USFDA), sildenafil enters the [...] Read more.

Sildenafil is a potent selective, reversible inhibitor of phosphodiesterase type 5 (PDE5) approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. Whilst twenty years have passed since its original approval by the US Food and Drug Administration (USFDA), sildenafil enters the fourth industrial era catalyzing the treatment advances against erectile dysfunction and pulmonary hypertension. The plethora of detailed clinical data accumulated and the two sildenafil analogues marketed, namely tadalafil and vardenafil, signify the relevant therapeutic and commercial achievements. The pharmacokinetic and pharmacodynamic behavior of the drug appears complex, interdependent and of critical importance whereas the treatment of special population cohorts is considered. The diversity of the available formulation strategies and their compatible administration routes, extend from tablets to bolus suspensions and from per os to intravenous, respectively, inheriting the associated strengths and weaknesses. In this comprehensive review, we attempt to elucidate the multi-disciplinary elements spanning the knowledge fields of chemical synthesis, physicochemical properties, pharmacology, clinical applications, biopharmaceutical profile, formulation approaches for different routes of administration and analytical strategies, currently employed to guide the development of sildenafil-based compositions. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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14 pages, 1726 KiB

Open AccessFeature PaperEditor’s ChoiceReview

2020 FDA TIDES (Peptides and Oligonucleotides) Harvest

by Othman Al Musaimi, Danah Al Shaer, Fernando Albericio and Beatriz G. de la Torre

Pharmaceuticals 2021, 14(2), 145; https://doi.org/10.3390/ph14020145 - 11 Feb 2021

Cited by 56 | Viewed by 5964

Abstract

2020 has been an extremely difficult and challenging year as a result of the coronavirus disease 2019 (COVID-19) pandemic and one in which most efforts have been channeled into tackling the global health crisis. The US Food and Drug Administration (FDA) has approved [...] Read more.

2020 has been an extremely difficult and challenging year as a result of the coronavirus disease 2019 (COVID-19) pandemic and one in which most efforts have been channeled into tackling the global health crisis. The US Food and Drug Administration (FDA) has approved 53 new drug entities, six of which fall in the peptides and oligonucleotides (TIDES) category. The number of authorizations for these kinds of drugs has been similar to that of previous years, thereby reflecting the consolidation of the TIDES market. Here, the TIDES approved in 2020 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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15 pages, 1847 KiB

Open AccessReview

2019 FDA TIDES (Peptides and Oligonucleotides) Harvest

by Danah Al Shaer, Othman Al Musaimi, Fernando Albericio and Beatriz G. de la Torre

Pharmaceuticals 2020, 13(3), 40; https://doi.org/10.3390/ph13030040 - 5 Mar 2020

Cited by 55 | Viewed by 9141

Abstract

2019 has been an excellent year in terms of peptides and oligonucleotides (TIDES) approved by the FDA. Despite the drop in the number of total drugs approved by the FDA in 2019 in comparison with 2018 (48 vs. 59), the total number of [...] Read more.

2019 has been an excellent year in terms of peptides and oligonucleotides (TIDES) approved by the FDA. Despite the drop in the number of total drugs approved by the FDA in 2019 in comparison with 2018 (48 vs. 59), the total number of TIDES authorized increased (seven vs. three). Year after year, TIDES are increasingly present in therapy, as imaging agents, theragnostic and constituent moieties of other complex drugs, such as antibody drug conjugates. This means a consolidation of these kinds of drugs in the pharmaceutical arena, paving the way in the coming years for the approval of others for diverse medical indications. Here the TIDES approved in 2019 are analyzed in terms of chemical structure, medical target, mode of action, and adverse effects. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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12 pages, 1023 KiB

Open AccessReview

[⁶⁸Ga]Ga-DOTA-TOC: The First FDA-Approved ⁶⁸Ga-Radiopharmaceutical for PET Imaging

by Ute Hennrich and Martina Benešová

Pharmaceuticals 2020, 13(3), 38; https://doi.org/10.3390/ph13030038 - 3 Mar 2020

Cited by 107 | Viewed by 11875

Abstract

In the United States, [⁶⁸Ga]Ga-DOTA-TOC has been approved by the Food and Drug Administration (FDA) in 2019 as the first ⁶⁸Ga-radiopharmaceutical for imaging of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors while employing positron emission tomography (PET). In Europe (Austria, [...] Read more.

In the United States, [⁶⁸Ga]Ga-DOTA-TOC has been approved by the Food and Drug Administration (FDA) in 2019 as the first ⁶⁸Ga-radiopharmaceutical for imaging of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors while employing positron emission tomography (PET). In Europe (Austria, Germany, France), [⁶⁸Ga]Ga-DOTA-TOC was already approved back in 2016. This radiopharmaceutical combines the radionuclide ⁶⁸Ga with the somatostatin analogue DOTA-TOC for specific imaging of tumor cells expressing SSTRs. Such a targeting approach can also be used for therapy planning in the case of both localized as well as disseminated disease and potentially for the evaluation of treatment response. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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8 pages, 1840 KiB

Open AccessReview

Lutathera^®: The First FDA- and EMA-Approved Radiopharmaceutical for Peptide Receptor Radionuclide Therapy

by Ute Hennrich and Klaus Kopka

Pharmaceuticals 2019, 12(3), 114; https://doi.org/10.3390/ph12030114 - 29 Jul 2019

Cited by 248 | Viewed by 17108

Abstract

As the first radiopharmaceutical for Peptide Receptor Radionuclide Therapy (PRRT), Lutathera^® was approved by the EMA in 2017 and the FDA in 2018 for the treatment of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors. Using the concept of PRRT, Lutathera^® combines [...] Read more.

As the first radiopharmaceutical for Peptide Receptor Radionuclide Therapy (PRRT), Lutathera^® was approved by the EMA in 2017 and the FDA in 2018 for the treatment of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors. Using the concept of PRRT, Lutathera^® combines the radionuclide ¹⁷⁷Lu with the somatostatin analogue DOTA-TATE, thus delivering ionizing radiation specifically to tumor cells expressing somatostatin receptors. As a result, DNA single- and double-strand breaks are provoked, in case of double-strand breaks leading to cell death of the tumor and its SSTR-positive lesions. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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49 pages, 1247 KiB

Open AccessReview

Psychotropic Drugs for the Management of Chronic Pain and Itch

by Daria A. Belinskaia, Mariia A. Belinskaia, Oleg I. Barygin, Nina P. Vanchakova and Natalia N. Shestakova

Pharmaceuticals 2019, 12(2), 99; https://doi.org/10.3390/ph12020099 - 24 Jun 2019

Cited by 29 | Viewed by 9131

Abstract

Clinical observations have shown that patients with chronic neuropathic pain or itch exhibit symptoms of increased anxiety, depression and cognitive impairment. Such patients need corrective therapy with antidepressants, antipsychotics or anticonvulsants. It is known that some psychotropic drugs are also effective for the [...] Read more.

Clinical observations have shown that patients with chronic neuropathic pain or itch exhibit symptoms of increased anxiety, depression and cognitive impairment. Such patients need corrective therapy with antidepressants, antipsychotics or anticonvulsants. It is known that some psychotropic drugs are also effective for the treatment of neuropathic pain and pruritus syndromes due to interaction with the secondary molecular targets. Our own clinical studies have identified antipruritic and/or analgesic efficacy of the following compounds: tianeptine (atypical tricyclic antidepressant), citalopram (selective serotonin reuptake inhibitor), mianserin (tetracyclic antidepressant), carbamazepine (anticonvulsant), trazodone (serotonin antagonist and reuptake inhibitor), and chlorprothixene (antipsychotic). Venlafaxine (serotonin-norepinephrine reuptake inhibitor) is known to have an analgesic effect too. The mechanism of such effect of these drugs is not fully understood. Herein we review and correlate the literature data on analgesic/antipruritic activity with pharmacological profile of these compounds. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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14 pages, 792 KiB

Open AccessReview

Long-Acting Anti-HIV Drugs Targeting HIV-1 Reverse Transcriptase and Integrase

by Kamal Singh, Stefan G. Sarafianos and Anders Sönnerborg

Pharmaceuticals 2019, 12(2), 62; https://doi.org/10.3390/ph12020062 - 20 Apr 2019

Cited by 29 | Viewed by 7516

Abstract

One of the major factors contributing to HIV-1 drug resistance is suboptimal adherence to combination antiretroviral therapy (cART). Currently, recommended cART for HIV-1 treatment is a three-drug combination, whereas the pre-exposure prophylaxis (PrEP) regimens consist of one or two antivirals. Treatment regimens require [...] Read more.

One of the major factors contributing to HIV-1 drug resistance is suboptimal adherence to combination antiretroviral therapy (cART). Currently, recommended cART for HIV-1 treatment is a three-drug combination, whereas the pre-exposure prophylaxis (PrEP) regimens consist of one or two antivirals. Treatment regimens require adherence to a once or twice (in a subset of patients) daily dose. Long-acting formulations such as injections administered monthly could improve adherence and convenience, and thereby have potential to enhance the chances of expected outcomes, although long-lasting drug concentrations can also contribute to clinical issues like adverse events and development of drug resistance. Globally, two long-acting antivirals have been approved, and fifteen are in clinical trials. More than half of investigational long-acting antivirals target HIV-1 reverse transcriptase (HIV-1 RT) and/or integrase (HIV-1 IN). Here, we discuss the status and potential of long-acting inhibitors, including rilpivirine (RPV), dapivirine (DPV), and 4-ethynyl-2-fluoro-2-deoxyadenosine (EFdA; also known as MK-8591), which target RT, and cabotegravir (CAB), which targets IN. The outcomes of various clinical trials appear quite satisfactory, and the future of long-acting HIV-1 regimens appears bright. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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6 pages, 877 KiB

Open AccessReview

2018 FDA Tides Harvest

by Danah Al Shaer, Othman Al Musaimi, Fernando Albericio and Beatriz G. de la Torre

Pharmaceuticals 2019, 12(2), 52; https://doi.org/10.3390/ph12020052 - 5 Apr 2019

Cited by 42 | Viewed by 7597

Abstract

In 2018, the United States Food and Drug Administration (FDA) approved a total of 59 new drugs, three of them (5%) are TIDES (or also, -tides), two oligonucleotides and one peptide. Herein, the three TIDES approved are analyzed in terms of medical target, [...] Read more.

In 2018, the United States Food and Drug Administration (FDA) approved a total of 59 new drugs, three of them (5%) are TIDES (or also, -tides), two oligonucleotides and one peptide. Herein, the three TIDES approved are analyzed in terms of medical target, mode of action, chemical structure, and economics. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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11 pages, 1059 KiB

Open AccessBrief Report

Is There a Role for the Therapeutic Drug Monitoring of Colistin? An Overview

by Maria-Paula Avila, Tatiana Pacheco, Sara Arias, Rosa-Helena Bustos, Julio-Cesar Garcia and Diego Jaimes

Pharmaceuticals 2020, 13(3), 42; https://doi.org/10.3390/ph13030042 - 6 Mar 2020

Cited by 9 | Viewed by 4266

Abstract

Colistin is used as a last-line antibiotic for the treatment of Gram-negative multiresistant bacteria. Due to its high nephrotoxicity, Therapeutic Drug Monitoring (TDM) is recommended for dose adjustment. We aimed to evaluate the available evidence of TDM in patients given colistin to treat [...] Read more.

Colistin is used as a last-line antibiotic for the treatment of Gram-negative multiresistant bacteria. Due to its high nephrotoxicity, Therapeutic Drug Monitoring (TDM) is recommended for dose adjustment. We aimed to evaluate the available evidence of TDM in patients given colistin to treat Gram-negative infections. In this paper, we offer an overview, using an electronic search of the literature (published up to June 2019, without language restrictions) that compares the clinical outcomes and measurements of colistin TDM. Ultimately, the Therapeutic Drug Monitoring (TDM) of colistin in Plasma could prevent nephrotoxicity risk. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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7 pages, 2374 KiB

Open AccessBrief Report

Tafenoquine: A 2018 Novel FDA-Approved Prodrug for the Radical Cure of Plasmodium vivax Malaria and Prophylaxis of Malaria

by Annie Mayence and Jean Jacques Vanden Eynde

Pharmaceuticals 2019, 12(3), 115; https://doi.org/10.3390/ph12030115 - 30 Jul 2019

Cited by 14 | Viewed by 7201

Abstract

Tafenoquine (an 8-aminoquinoline) was approved by the Food and Drug Administration (FDA) in 2018 for the radical cure of Plasmodium vivax malaria and preventive action against malaria. Despite the fact that the mechanism of action of the drug remains unclear, all studies indicated [...] Read more.

Tafenoquine (an 8-aminoquinoline) was approved by the Food and Drug Administration (FDA) in 2018 for the radical cure of Plasmodium vivax malaria and preventive action against malaria. Despite the fact that the mechanism of action of the drug remains unclear, all studies indicated that a metabolite is responsible for its efficacy. Routes for the preparation of the drug are described. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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6 pages, 539 KiB

Open AccessBrief Report

Tegsedi (Inotersen): An Antisense Oligonucleotide Approved for the Treatment of Adult Patients with Hereditary Transthyretin Amyloidosis

by Luís Gales

Pharmaceuticals 2019, 12(2), 78; https://doi.org/10.3390/ph12020078 - 21 May 2019

Cited by 40 | Viewed by 8020

Abstract

Tegsedi (Inotersen) is a chemically modified antisense oligonucleotide that inhibits the hepatic production of transthyretin (TTR). Several single-point mutations in TTR destabilize its structure, leading to the aggregation and accumulation of amyloid deposits in the nervous system, heart, kidneys and eyes. In July [...] Read more.

Tegsedi (Inotersen) is a chemically modified antisense oligonucleotide that inhibits the hepatic production of transthyretin (TTR). Several single-point mutations in TTR destabilize its structure, leading to the aggregation and accumulation of amyloid deposits in the nervous system, heart, kidneys and eyes. In July 2018, Tegsedi was approved by the European Commission for use in adults with stage one and two polyneuropathies. Later on, in October 2018, the FDA and Health Canada also approved its use for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults in the U.S. and Canada. Tegsedi was developed by Ionis Pharmaceuticals, the company that holds the global marketing license, together with its subsidiary Akcea Therapeutics. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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7 pages, 1427 KiB

Open AccessBrief Report

Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases

by Daniel A. Rodrigues, Fernanda S. Sagrillo and Carlos A. M. Fraga

Pharmaceuticals 2019, 12(2), 69; https://doi.org/10.3390/ph12020069 - 6 May 2019

Cited by 53 | Viewed by 7017

Abstract

Duvelisib (Copiktra^®) is a dual inhibitor of phosphoinositide 3-kinases (PI3Kδ and PI3Kγ). In 2018, duvelisib was first approved by the Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL)/ small lymphocytic [...] Read more.

Duvelisib (Copiktra^®) is a dual inhibitor of phosphoinositide 3-kinases (PI3Kδ and PI3Kγ). In 2018, duvelisib was first approved by the Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma (SLL) after at least two prior therapies. Duvelisib has also been approved under accelerated track for relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. In this review, we provide a series of information about duvelisib, such as the development of clinical trials for LLC/SLL and FL and the steps used for its synthesis. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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9 pages, 982 KiB

Open AccessBrief Report

Omadacycline: A Newly Approved Antibacterial from the Class of Tetracyclines

by Fernando Durães and Emília Sousa

Pharmaceuticals 2019, 12(2), 63; https://doi.org/10.3390/ph12020063 - 21 Apr 2019

Cited by 20 | Viewed by 7875

Abstract

Omadacycline (Nuzyra®) is a new aminomethylcycline, approved by the U. S. Food and Drug Administration in 2018, as a tetracycline antibacterial. It can be used in community-acquired pneumonia and in acute bacterial skin and skin-structure infections. It was developed and is commercialized by [...] Read more.

Omadacycline (Nuzyra®) is a new aminomethylcycline, approved by the U. S. Food and Drug Administration in 2018, as a tetracycline antibacterial. It can be used in community-acquired pneumonia and in acute bacterial skin and skin-structure infections. It was developed and is commercialized by Paratek Pharmaceuticals. It is a semisynthetic compound, derived from minocycline, capable of evading widely distributed efflux and target protection antibacterial resistance mechanisms and has demonstrated activity in a broad spectrum of bacteria. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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7 pages, 1010 KiB

Open AccessBrief Report

Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases

by Annie Mayence and Jean Jacques Vanden Eynde

Pharmaceuticals 2019, 12(1), 37; https://doi.org/10.3390/ph12010037 - 12 Mar 2019

Cited by 38 | Viewed by 8849

Abstract

In 2018, Baricitinib was approved by the Food and Drig Administration (FDA) for the treatment of rheumatoid arthritis. Baricitinib exerts its action by targeting Janus kinases (JAK). In this study, we describe the necessary steps for preparing the drug using two alternative routes. [...] Read more.

In 2018, Baricitinib was approved by the Food and Drig Administration (FDA) for the treatment of rheumatoid arthritis. Baricitinib exerts its action by targeting Janus kinases (JAK). In this study, we describe the necessary steps for preparing the drug using two alternative routes. Full article

(This article belongs to the Special Issue The Story of Successful Drugs and Recent FDA-Approved Molecules)

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