Article
Pharmacology & Pharmacy
Morris Muliaditan, Oscar Della Pasqua
Summary: The study aims to develop a drug-disease model that distinguishes between drug- and system-specific properties, providing theoretical basis for the clinical application of anti-tubercular drugs.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Infectious Diseases
Enyu Tong, Ying Zhou, Zhengwei Liu, Yelei Zhu, Mingwu Zhang, Kunyang Wu, Junhang Pan, Jianmin Jiang
Summary: This study aimed to determine the prevalence and molecular characterization of bedaquiline resistance among rifampicin-resistant tuberculosis isolates in Zhejiang, China. The results showed that bedaquiline exhibited strong antibacterial activity against rifampicin-resistant tuberculosis isolates, and the Rv0678 gene was identified as the primary mechanism contributing to bedaquiline resistance in Zhejiang, China.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Pharmacology & Pharmacy
Jeanine E. Ballard, Parul S. Pall, Joshua Vardigan, Fuqiang Zhao, Marie A. Holahan, Xiaoping Zhou, Nina Jochnowitz, Richard L. Kraus, Rebecca M. Klein, Darrell A. Henze, Andrea K. Houghton, Christopher S. Burgey, Christopher Gibson, Arie Struyk
Summary: MK-2075 is a small-molecule selective inhibitor of the NaV1.7 channel investigated for postoperative pain treatment. A translational strategy was developed to quantitatively relate drug exposure, target modulation, and pharmacological response in preclinical animal models, informing clinical study design and decision criteria. Integration of pharmacokinetic and pharmacodynamic data from preclinical species guided dose prediction and target modulation assessment for potential clinical efficacy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Microbiology
Walter Yamada, Sarah Kim, Mohammed Almoslem, Soyoung Kim, Jenny Myrick, Jocelyn Nole, Brandon Duncanson, Arnold Louie, Charles A. Peloquin, Stephan Schmidt, George L. Drusano, Michael Neely
Summary: The study utilized a model-informed strategy to test the efficacy of drug combinations against nonreplicating persister (NRP) phenotype of Mycobacterium tuberculosis. The results showed that the two-drug combination of pretomanid and moxifloxacin effectively eradicated Mtb, while the addition of bedaquiline as a third drug significantly shortened the time to total bacterial suppression.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Simon E. Koele, Stijn W. van Beek, Gary Maartens, James C. M. Brust, Elin M. Svensson
Summary: Interruption of treatment is common in drug-resistant tuberculosis patients. Restarting treatment with bedaquiline without a loading dose after an interruption could increase the risk of suboptimal treatment outcome and resistance development. This study identified suitable loading dose strategies for bedaquiline restart based on simulation and recommended reloading periods of 3 days, 1 week, and 2 weeks for interruptions of different durations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Krina Mehta, Tingjie Guo, Piet H. Van der Graaf, J. G. Coen van Hasselt
Summary: A mechanistic modeling framework was developed to compare the efficacy of current and alternative BPaL treatment strategies, and the simulations suggested that comparable efficacy can be achieved using alternative dosing regimens.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Infectious Diseases
Thi Mai Phuong Nguyen, Thi Hai Minh Le, Corinne Simone Collette Merle, Debora Pedrazzoli, Nhat Linh Nguyen, Tom Decroo, Binh Hoa Nguyen, Thi Thanh Thuy Hoang, Viet Nhung Nguyen
Summary: This study evaluated the safety and effectiveness of a modified short treatment regimen (mSTR) consisting of 5 drugs. The results showed a high treatment success rate and suggested that the mSTR could replace the standard 7-drug regimen. Although adverse events occurred in some patients, they were mostly manageable.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Mohammadreza Salehi, Farnaz Farbod, Hossein Khalili, Hamid Rahmani, Sirous Jafari, Ali Abbasi
Summary: This study compared the efficacy and safety of higher and standard doses of rifampicin in combination with doxycycline in patients with brucellosis. The clinical response was significantly higher in the high-dose group compared to the standard-dose group, without further adverse events. If these findings are confirmed in future studies, higher doses of rifampicin may be recommended for the treatment of brucellosis.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Sarah Kim, Arnold Louie, George L. Drusano, Mohammed Almoslem, Soyoung Kim, Jenny Myrick, Jocelyn Nole, Brandon Duncanson, Charles A. Peloquin, Charles A. Scanga, Walter Yamada, Michael Neely, Stephan Schmidt
Summary: This study evaluated the efficacy of clofazimine (CFZ)-containing two-drug regimens with pretomanid (PMD), bedaquiline (BDQ), or linezolid (LZD) for the treatment of tuberculosis. The results showed synergistic effects when CFZ was combined with PMD, BDQ, and LZD against Mycobacterium tuberculosis in different metabolic states. The combination regimens demonstrated greater bacterial kill than the individual drugs. CFZ alone had the weakest antimicrobial efficacy among the evaluated drugs, and the correlation between the mode of interaction and the extent of bacterial kill was not significant.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Shao-Jun Zhang, Yan Yang, Wen-Wen Sun, Zhong-Shun Zhang, He-Ping Xiao, Yu-Ping Li, Zhe-Min Zhang, Lin Fan
Summary: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.
BMC INFECTIOUS DISEASES
(2022)
Article
Respiratory System
Lindsey H. M. te Brake, Veronique de Jager, Kim Narunsky, Naadira Vanker, Elin M. Svensson, Patrick P. J. Phillips, Stephen H. Gillespie, Norbert Heinrich, Michael Hoelscher, Rodney Dawson, Andreas H. Diacon, Rob E. Aamoutse, Martin J. Boeree
Summary: The study evaluated the safety, tolerability, pharmacokinetics, and early bactericidal activity of increasing doses of rifampicin in treatment-naive adult smear-positive patients with tuberculosis. While the 50mg/kg dose showed an increased bactericidal effect, it was not well tolerated, leading to treatment discontinuations, whereas the 40mg/kg dose was well tolerated and selected for further evaluation.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Microbiology
Jian Du, Jingtao Gao, Yanhong Yu, Qingfeng Li, Guanghong Bai, Wei Shu, Mengqiu Gao, Yuhong Liu, Lu Wang, Yufeng Wang, Zhongtan Xue, Fengmin Huo, Liang Li, Yu Pang
Summary: In this retrospective study in China, researchers aimed to determine the prevalence of linezolid resistance among MDR-TB patients, monitor changes in linezolid susceptibility during treatment, and explore molecular mechanisms of resistance. They found that 6.9% of patients had linezolid resistance, with a higher rate in those previously exposed to the drug. The most common genetic mutation conferring resistance was a Cys154Arg substitution in the ribosomal protein L3.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Laura N. Jeffreys, Alison Ardrey, Taghreed A. Hafiz, Lauri-Anne Dyer, Ashley J. Warman, Nada Mosallam, Gemma L. Nixon, Nicholas E. Fisher, W. David Hong, Suet C. Leung, Ghaith Aljayyoussi, Jaclyn Bibby, Deepak V. Almeida, Paul J. Converse, Nader Fotouhi, Neil G. Berry, Eric L. Nuermberger, Anna M. Upton, Paul M. O'Neill, Stephen A. Ward, Giancarlo A. Biagini
Summary: This study successfully expressed Mycobacterium tuberculosis cytochrome bd oxidase and identified a series of inhibitors that can effectively suppress bacterial growth, suggesting their potential as antitubercular agents.
ACS INFECTIOUS DISEASES
(2023)
Article
Immunology
Elise D. Pieterman, Lina Keutzer, Aart van der Meijden, Sanne van den Berg, Han Wang, Matthew D. Zimmerman, Ulrika S. H. Simonsson, Hannelore Bax, Jurriaan E. M. de Steenwinkel
Summary: The study compared the efficacy of an all oral drug regimen (BDL) with a standard regimen (HRZE) on the mycobacterial load in the lungs and spleen of tuberculosis-infected mice, showing that BDL was more effective and could be a valuable option for the treatment of drug-resistant tuberculosis.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Christian Etschmann, Regina Scherliess
Summary: Lung tuberculosis is a deadly infectious disease that affects millions of people worldwide. Despite being treatable, many patients only achieve sub-therapeutic concentrations of antibiotics in the infected lung tissue, leading to an alarming number of multi drug resistant tuberculosis cases each year. In this study, researchers demonstrate the effectiveness of using softpellets, engineered dry powder agglomerates, to deliver high doses of antibiotics directly to the lungs. Furthermore, a new process design called vibro-pelletisation for producing softpellets is introduced.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Editorial Material
Pharmacology & Pharmacy
James N. Fullerton, Oscar Della Pasqua, Robert Likic
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Salvatore D'Agate, Chandrashekhar Chavan, Michael Manyak, Juan Manuel Palacios-Moreno, Matthias Oelke, Martin C. Michel, Claus G. Roehrborn, Oscar Della Pasqua
Summary: By analyzing pooled data, it was found that the use of dutasteride and tamsulosin-dutasteride combination therapy significantly reduced the baseline risk of acute urinary retention or BPH-related surgery. The study also highlighted the contribution of different baseline characteristics to the risk of these events, and emphasized that tamsulosin monotherapy has no impact on long-term risk for individuals.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Urology & Nephrology
Salvatore D'Agate, Chandrashekhar Chavan, Michael Manyak, Juan Manuel Palacios-Moreno, Matthias Oelke, Martin C. Michel, Claus G. Roehrborn, Oscar Della Pasqua
Summary: The study evaluated the effect of delayed start of combination therapy with dutasteride and tamsulosin on the risk of acute urinary retention or BPH-related surgery in patients with moderate-to-severe LUTS at risk of disease progression. The results showed that starting combination therapy before 6 months significantly reduced the risk of AUR/S in these patients.
WORLD JOURNAL OF UROLOGY
(2021)
Review
Pharmacology & Pharmacy
Annette S. Gross, Anya C. Harry, Christine S. Clifton, Oscar Della Pasqua
Summary: Although the number of countries participating in pivotal trials has increased, there has not been a substantial increase in the diversity of clinical trial populations. Efforts have been made by regulatory agencies, patient advocacy groups, and clinical researchers to ensure representation of patient populations in clinical trials, but challenges remain.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Morris Muliaditan, Oscar Della Pasqua
Summary: The study aims to develop a drug-disease model that distinguishes between drug- and system-specific properties, providing theoretical basis for the clinical application of anti-tubercular drugs.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Glauco Henrique Balthazar Nardotto, Valdes Roberto Bollela, Adriana Rocha, Oscar Della Pasqua, Vera Lucia Lanchote
Summary: This study aimed to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to first-line anti-tubercular drugs in patients with tuberculosis. The results suggest that there is no significant pharmacokinetic interaction between the selected antivirals and first-line anti-tubercular drugs in patients with TB, and HIV coinfection itself does not appear to have any effect on the plasma exposure to these drugs.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Elisa Borella, Sean Oosterholt, Paolo Magni, Oscar Della Pasqua
Summary: The aim of this study was to develop a drug-disease model describing the impact of iron overload on patients with transfusion-dependent hemoglobinopathies and to investigate the role of individual differences in chelation therapy with deferiprone or deferasirox. The results showed that deferiprone had a significantly larger effect on iron elimination rate compared to deferasirox.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Lindsey Ingleby-Talecki, Sven C. van Dijkman, Sean P. Oosterholt, Oscar Della Pasqua, Christina Winter, Marianne Cunnington, Linda Rebar, Sergio Forero-Schwanhaeuser, Vickas Patel, James A. Cooper, Anthony Bahinski, Khuram W. Chaudhary
Summary: Lamotrigine is a medication used for the treatment of epilepsy and bipolar disorder. It inhibits sodium channels in the brain to reduce neuronal firing and pathological release of glutamate. Clinical studies have shown that lamotrigine does not slow cardiac conduction and is safe for patients suffering from epilepsy and bipolar disorder.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Morris Muliaditan, Donato Teutonico, Fatima Ortega-Muro, Santiago Ferrer, Oscar Della Pasqua
Summary: This study used whole-body physiologically-based pharmacokinetic (PBPK) modeling based on plasma data in mice to predict lung exposure to anti-tubercular drugs in humans. The predicted lung exposures were comparable to plasma levels for isoniazid and pyrazinamide, but higher than plasma for ethambutol. This suggests that combining plasma pharmacokinetics with PBPK modeling can be used to derive lung tissue exposure in mice and humans during the early optimization phase of tuberculosis drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Janna K. Duong, Romina A. Nand, Aarti Patel, Oscar Della Pasqua, Annette S. Gross
Summary: This study developed a PBPK model to describe the pharmacokinetics of clopidogrel and its metabolites in European and Japanese populations, and found that CYP2C19 activity has an effect on the pharmacokinetics in both populations.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Pharmacology & Pharmacy
Flora T. Musuamba, S. Y. Amy Cheung, Pieter Colin, Elin H. Davies, Jeffrey S. Barret, Francesco Pappalardo, Michael Chappell, Jean-Michel Dogne, Adriana Ceci, Oscar Della Pasqua, Ine S. Rusten
Summary: The benefit/risk balance is the most important question when considering market access for medicinal products. This assessment involves evaluating efficacy, safety, dose selection, pharmacology, and drug quality. However, there is currently no systematic approach to assess and establish the acceptability of alternative methods and data sources, leading to regulatory skepticism toward new data types and methods. To mitigate uncertainties in efficacy and safety characterization, a data-knowledge backbone is needed. This white paper proposes an ecosystem based on a repository, high-quality standards, and credibility assessment for better regulatory decision making.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Sean Oosterholt, Ian D. D. Pavord, Guy Brusselle, Arzu Yorgancioglu, Paulo M. M. Pitrez, Abhijith Pg, Chirag Teli, Oscar Della Pasqua
Summary: Limited understanding of the association between clinical and demographic characteristics and exacerbation risk in patients with moderate-to-severe asthma. This study assessed the relationship between baseline characteristics and exacerbation risk in clinical trial patients with varying levels of symptom control. Personalized interventions are important in managing moderate-to-severe asthma patients.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Dave Singh, Sean Oosterholt, Ian Pavord, Gabriel Garcia, P. G. Abhijith, Oscar Della Pasqua
Summary: The study aimed to demonstrate that individual baseline characteristics can affect the risk of exacerbation and treatment response in patients receiving inhaled corticosteroid therapy. Results showed that poor symptom control, limited lung function, obesity, smoking, and sex are associated with an increase in the incidence of asthma attacks. Additionally, combination therapy with fluticasone propionate/salmeterol resulted in a 10% lower incidence of attacks compared to budesonide/formoterol. These factors should be considered for personalized management of moderate-severe asthma patients.
ADVANCES IN THERAPY
(2023)
Article
Pharmacology & Pharmacy
Paul Healy, Luka Verrest, Mariagrazia Felisi, Adriana Ceci, Oscar Della Pasqua, GAPP Consortium
Summary: This study uses clinical trial simulations (CTS) as a tool to optimize doses and protocol design for pediatric patients with chronic pain. The study uses pharmacokinetic modeling and CTS to describe the pharmacokinetics of gabapentin and tramadol in this population. The results suggest the need for dose titration and provide recommended doses for different weight ranges.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)