Article
Pharmacology & Pharmacy
Hongping Xiang, Hong Zhou, Jing Zhang, Yongfeng Sun, Yirong Wang, Yong Han, Jie Cai
Summary: This study investigated the pharmacokinetics of MMFdt combined with tacrolimus in Chinese adult heart transplant recipients and developed a practical method for estimating MPA-AUC(0-12h) using a limited sampling strategy (LSS). The results showed significant inter-individual variability in PK parameters after MMFdt administration, but no significant differences between MMFdt and MMFc. A four-point LSS equation using concentrations at 0.5, 2, 4, and 6 hours was recommended for estimating MPA-AUC(0-12h) during the early period after transplantation, with good applicability in both internal and external validations.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Felicien Le Louedec, Fanny Gallais, Fabienne Thomas, Melanie White-Koning, Ben Allal, Caroline Protin, Loic Ysebaert, Etienne Chatelut, Florent Puisset
Summary: The study found that a limited sampling strategy using the T0-1-2-4 design can accurately estimate ibrutinib exposure, with good accuracy even when removing the 1-hour or 2-hour sampling points. The correlation between actual AUC(IBRU) and C-min, C-ss was poor, and joint analysis of dihydrodiol-ibrutinib metabolite concentrations did not improve predictive performance. At least three samples within the pre-dose and 4-hour post-dose period are necessary for accurate estimation of ibrutinib exposure.
Article
Immunology
Jihyun Lee, Giwon Choi, Seungwon Yang, Jung-Eun Ha, Eun Sun Kim, Jong Sun Park, Kyunghoon Lee, Junghan Song, Jae Ho Lee, Jangik Lee
Summary: A limited sampling strategy (LSS) was developed to estimate isoniazid exposure in Korean tuberculosis patients, considering NAT2 genotypes. Results showed varying pharmacokinetics of isoniazid among different genotypes, with formulas constructed to estimate exposure based on concentration-time points. Pre-dose NAT2 genotyping may be valuable for optimal isoniazid dosing in patients.
Article
Pharmacology & Pharmacy
Lana Tran, Mina Nikanjam, Edmund V. Capparelli, Joseph S. Bertino, Anne N. Nafziger, Angela D. M. Kashuba, Sandrine Turpault, Joseph D. Ma
Summary: This study evaluated S-warfarin limited sampling strategy with a population PK approach to estimate CYP2C9 activity in healthy adults. The results showed that LSMs at 48 hr, 72 hr, and 2-timepoints were within acceptable limits for R-2, %MPE, %MAE, and %RMSE under CYP2C9 constitutive conditions, but had unacceptable errors during CYP2C9 induction.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Medical Laboratory Technology
Joseph Piscitelli, Mina Nikanjam, Edmund V. Capparelli, Chelsea L. Blaquera, Scott R. Penzak, Thomas D. Nolin, Mary F. Paine, Joseph D. Ma
Summary: This study evaluated a limited sampling strategy to estimate plasma fexofenadine exposure as an index of P-gp and OATP activities. However, identifying a novel fexofenadine limited sampling model remains elusive for future transporter-mediated drug-drug interaction studies in healthy adults.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Pharmacology & Pharmacy
Jeana Jacob, Sumith K. Mathew, Raju Titus Chacko, Blessed Winston Aruldhas, Ashish Singh, Ratna Prabha, Binu Susan Mathew
Summary: This study aimed to determine the pharmacokinetic exposure of 5-FU and DHFU in patients with gastrointestinal malignancy, and develop a simplified strategy to assist in therapeutic drug management for dose optimization. Results showed a higher proportion of patients had exposures within the therapeutic range in dose 3 compared to dose 1 with 5-FU, and a limited sampling strategy accurately predicted the total area under the curve of 5-FU. The study suggested the measurement of DHFU could be a phenotypical measure of dihydropyrimidine dehydrogenase enzyme activity in the absence of genotype testing.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ida Kuhlmann, Sidsel Arnspang Pedersen, Peter Skov Esbech, Tore Bjerregaard Stage, Mette Marie Hougaard Christensen, Kim Brosen
Summary: The study supports the feasibility of using the 2-point LSS algorithm in large pharmacokinetic trials. There was significant interindividual variability in metformin AUC and CLrenal among the 212 healthy volunteers.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Infectious Diseases
Soedarsono Soedarsono, Rannissa Puspita Jayanti, Ni Made Mertaniasih, Tutik Kusmiati, Ariani Permatasari, Dwi Wahyu Indrawanto, Anita Nur Charisma, Rika Yuliwulandari, Nguyen Phuoc Long, Young-Kyung Choi, Pham Quang Hoa, Pham Vinh Hoa, Yong-Soon Cho, Jae-Gook Shin
Summary: In this study, a population pharmacokinetics model of isoniazid (INH) was developed for Indonesian patients with tuberculosis (TB), aiming to optimize pharmacotherapy through therapeutic drug monitoring (TDM). The study found that the NAT2 acetylator phenotype significantly affected the clearance of INH.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Microbiology
A. Facchin, N. Benyoub, V. Elie, S. Magreault, E. Jacqz-Aigrain
Summary: Valganciclovir is an antiviral agent used to prevent cytomegalovirus infection in renal transplant children. Therapeutic drug monitoring is still necessary to ensure optimal pharmacokinetic variability. This study developed and validated a limited sampling strategy for individualizing valganciclovir dosage in renal transplant children.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Xueyong Li, Bingqing Zhang, Yu Cheng, Maohua Chen, Hailing Lin, Binglin Huang, Wancai Que, Maobai Liu, Lili Zhou, Qinyong Weng, Hui Zhang, Hongqiang Qiu
Summary: This study validated the feasibility of limited sampling strategies (LSS) based on literature in predicting the concentration-time curve (AUC(ss,24h)) of polymyxin B (PMB), and explored the influence of infusion and sampling time errors on predictability.
Article
Chemistry, Analytical
Inna A. Galvidis, Yury A. Surovoy, Gleb S. Perevoznyuk, Sergei V. Tsarenko, Maksim A. Burkin
Summary: Polymyxins are used to treat multidrug resistant bacteria, but their narrow therapeutic window and variable pharmacokinetics in critically ill patients pose risks of toxicity and underdosing. This study explored methods for determining unbound polymyxin B (PMB) and proposed limited sampling strategies for clinical application. Rapid equilibrium dialysis demonstrated lower non-specific binding compared to ultrafiltration, making it a more reliable tool. The study also suggested using 1-3 sampling points and Bayesian estimation as an alternative approach.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Immunology
Agathe Beranger, Adrie Bekker, Belen P. Solans, Mark F. Cotton, Mark Mirochnick, Avy Violari, Jiajia Wang, Mae Cababasay, Lubbe Wiesner, Renee Browning, Jack Moye, Edmund Capparelli, Radojka M. Savic
Summary: INH dosing needs frequent adjustment to account for growth and maturation in low birth weight and preterm infants. Pharmacogenetics-based dosing regimens is the most powerful approach to deliver safe and equalized exposures for all infants, because NAT2 genotype highly impacts INH pharmacokinetic variability. Given the rapid growth and maturation in infants, INH dosing should be frequently adjusted to body weight.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Pharmacology & Pharmacy
Xipei Wang, Yijin Wu, Jinsong Huang, Songgui Shan, Mingjie Mai, Jiade Zhu, Min Yang, Dewei Shang, Zheng Wu, Jinhua Lan, Shilong Zhong, Min Wu
Summary: This study aimed to establish a strategy for estimating the area under the curve of mycophenolic acid (MPA) in heart transplant recipients and identify covariates affecting MPA pharmacokinetics. A PPK model was developed with three covariates, demonstrating the impact of proton pump inhibitors and estimated glomerular filtration rate on MPA exposure. Additionally, a linear equation using four time points was proposed as an alternative method for estimating MPA AUC(0-12h).
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Infectious Diseases
Alice Trentalange, Enrica Borgogno, Ilaria Motta, Miriam Antonucci, Veronica Pirriatore, Cecilia Costa, Giovanni Rossi, Ambra Barco, Amedeo De Nicolo, Pavilio Piccioni, Antonio D'Avolio, Stefano Bonora, Giovanni Di Perri, Andrea Calcagno
Summary: The study revealed that a majority of patients receiving first-line anti-TB treatment had suboptimal drug exposure, particularly for isoniazid and rifampin. Multivariate analysis identified higher doses/kg and other factors as potential causes for suboptimal drug exposure. Increased doses or therapeutic drug monitoring may be advised for selected patients.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Pharmacology & Pharmacy
Lisanne M. Geers, Dan Cohen, Laura M. Wehkamp, Hans J. van Wattum, Jos G. W. Kosterink, Anton J. M. Loonen, Daan J. Touw
Summary: This study aims to develop a limited sampling strategy using a population pharmacokinetic model to estimate the AUC of clozapine. The results suggest that a two-point sampling strategy can accurately estimate AUC(0-12h) and AUC(0-24h) in clinical practice. Compared to trough level monitoring, the limited sampling strategy provides a better prediction of clozapine exposure and occurrence of side effects, and the use of DBS samples simplifies the sample collection process.
THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY
(2022)
Review
Infectious Diseases
Milo Gatti, Federico Pea
Summary: This review evaluates the role of pharmacokinetic/pharmacodynamic (PK/PD) optimization of novel beta-lactams in the management of difficult-to-treat resistance (DTR) Gram-negative infections. The findings suggest that optimizing antimicrobial therapy with novel beta-lactams based on PK/PD concepts can maximize clinical efficacy and prevent resistance emergence. Establishing a coordinated multidisciplinary team and implementing personalized antimicrobial exposure optimization can be crucial for the management of DTR Gram-negative infections.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2023)
Article
Pediatrics
Giorgio Cozzi, Alberto Grillone, Elettra Zuliani, Manuela Giangreco, Chiara Zanchi, Giuseppe Abbracciavento, Egidio Barbi, Alessandro Amaddeo
Summary: This study compared adolescents' visits to a tertiary-level paediatric emergency department in Italy during the pre-pandemic year and the first and second years of the COVID-19 pandemic, focusing on mental health presentations. The results showed an increase in visits related to mental health problems in the second year of the pandemic, along with a sharp increase in suicide attempts and eating disorders.
FRONTIERS IN PEDIATRICS
(2023)
Article
Pharmacology & Pharmacy
Rossella Barone, Matteo Conti, Pier Giorgio Cojutti, Milo Gatti, Pierluigi Viale, Federico Pea
Summary: Dalbavancin (DBV) is a long-acting antistaphylococcal lypoglycopeptide increasingly used for long-term treatment of subacute and/or chronic infections. Population pharmacokinetic studies have shown that two 1500mg doses of DBV 1 week apart can effectively treat infections for weeks. This study developed and validated a fast and simple analytical method for measuring DBV concentrations in human plasma microsamples using Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry (ITD LC-MS/MS) technique.
Article
Microbiology
Milo Gatti, Bruno Viaggi, Gian Maria Rossolini, Federico Pea, Pierluigi Viale
Summary: Developing evidence-based algorithms for targeted antibiotic therapy in critically ill patients with Staphylococcus aureus infections was the objective of this study. By conducting literature searches and expert assessments, specific therapeutic options were proposed for different types of infections caused by methicillin-susceptible and methicillin-resistant Staphylococcus aureus.
Article
Microbiology
Pier Giorgio Cojutti, Aaron J. Heffernan, Thomas Tangden, Paola Della Siega, Carlo Tascini, Jason A. Roberts, Federico Pea
Summary: This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in kidney transplant patients. Ganciclovir concentrations and CMV viral loads were retrospectively obtained from kidney transplant patients. Monte Carlo simulations were conducted to assess the probability of attaining viral load targets, and a PK/PD model was devised.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Carla Troisi, Pier Giorgio Cojutti, Matteo Rinaldi, Cristiana Laici, Antonio Siniscalchi, Pierluigi Viale, Federico Pea
Summary: The aim of this study was to compare the daily dose of 24 h-continuous infusion meropenem when GFR was calculated using different equations. The results showed that using estimated GFR may lead to significant underestimation or overestimation of meropenem dosages, therefore dose adjustments should be based on measured creatinine clearance in critically ill patients.
Article
Pharmacology & Pharmacy
Chun Liu, Pier Giorgio Cojutti, Maddalena Giannella, Marcello Roberto, Beatrice Casadei, Gianluca Cristiano, Cristina Papayannidis, Nicola Vianelli, Pier Luigi Zinzani, Pierluigi Viale, Francesca Bonifazi, Federico Pea
Summary: CAR T-cell therapy may cause cytokine release syndrome (CRS) and acute kidney injury, potentially affecting the pharmacokinetics of beta-lactam drugs. This study found that the clearance of meropenem and piperacillin did not need to be reduced in CAR T-cell patients experiencing CRS.
Article
Infectious Diseases
Milo Gatti, Giacomo Fornaro, Zeno Pasquini, Andrea Zanoni, Michele Bartoletti, Pierluigi Viale, Federico Pea
Summary: This study investigated the impact of inflammation on voriconazole exposure in critically ill patients with COVID-associated pulmonary aspergillosis (CAPA). The results suggest that CRP values greater than 11.46 mg/dL and PCT values greater than 0.3 ng/mL may downregulate voriconazole metabolism and increase the risk of toxicity.
Article
Infectious Diseases
Rossella Barone, Matteo Conti, Beatrice Giorgi, Milo Gatti, Pier Giorgio Cojutti, Pierluigi Viale, Federico Pea
Summary: Meropenem (MRP)-Vaborbactam (VBR) is a novel beta-lactam/beta-lactamase inhibitor used for difficult-to-treat Gram-negative infections. Therapeutic drug monitoring (TDM) is necessary due to inter-individual variability. A fast and sensitive LC-MS/MS method was developed for quantifying MRP and VBR in 3 μL human plasma samples, and successfully applied to critically ill patients.
Article
Microbiology
Milo Gatti, Matteo Rinaldi, Cecilia Bonazzetti, Paolo Gaibani, Maddalena Giannella, Pierluigi Viale, Federico Pea
Summary: This study aimed to assess the relationship between joint pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion ceftazidime-avibactam and the microbiological outcome of difficult-to-treat resistant Gram-negative infections. The study found that optimized joint PK/PD target attainment could be a way to eradicate these infections and render combination therapy unnecessary.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Infectious Diseases
Alessandra Oliva, Francesco Giuseppe De Rosa, Malgorzata Mikulska, Federico Pea, Maurizio Sanguinetti, Carlo Tascini, Mario Venditti
Summary: Invasive Candida Infections (ICIs) have experienced significant changes in epidemiology, pathophysiology, and clinical manifestations in recent decades, including a shift towards non-albicans species and an increase in exogenous infections. The long-acting echinocandin rezafungin has shown potent in-vitro activity against Candida spp., including azole-resistant strains and C.auris.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2023)
Article
Pharmacology & Pharmacy
Milo Gatti, Federico Pea
Summary: With the increasing spread of infections caused by multidrug-resistant pathogens, tailoring antimicrobial therapies based on a "patient-centered" approach is crucial. Therapeutic drug monitoring (TDM) is a valuable method, but expert interpretation of TDM results is needed to enhance clinical usefulness. MD Clinical Pharmacologists can interpret TDM results of antimicrobials in real-time for tailoring therapy based on specific drug/pathogen and patient issues.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2023)
Article
Infectious Diseases
Pasquale Maria Berrino, Milo Gatti, Matteo Rinaldi, Eugenio Brunocilla, Pierluigi Viale, Federico Pea
Summary: This study explores the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin-tazobactam or meropenem monotherapy and microbiological outcome in urological patients with Gram-negative infections. The results demonstrate that optimizing beta-lactam treatment through real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program can achieve microbiological eradication in most cases.
Article
Infectious Diseases
Milo Gatti, Pierluigi Viale, Federico Pea
Summary: This study aimed to assess the distribution of individual ceftazidime-to-avibactam ratios in relation to renal function in patients receiving continuous infusion ceftazidime/avibactam treatment. The results showed a wide interindividual variability in ceftazidime-to-avibactam ratios, supporting the view that both ceftazidime and avibactam concentrations should be measured to evaluate pharmacokinetic/pharmacodynamic target attainment.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Altea Gallerani, Milo Gatti, Andrea Bedini, Stefania Casolari, Gabriella Orlando, Cinzia Puzzolante, Erica Franceschini, Marianna Menozzi, Antonella Santoro, Nicole Barp, Sara Volpi, Alessandra Soffritti, Federico Pea, Cristina Mussini, Marianna Meschiari
Summary: This retrospective case series reports on the use of dalbavancin in the treatment of cardiovascular prosthetic infections. The results show that dalbavancin is effective and well-tolerated in this setting. Monitoring drug concentrations can individualize dosing and dosing intervals, further improving clinical outcomes.
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Infectious Diseases
Roberta Gagliardini, Alessandro Tavelli, Stefano Rusconi, Sergio Lo Caputo, Vincenzo Spagnuolo, Maria Mercedes Santoro, Andrea Costantini, Alessandra Vergori, Franco Maggiolo, Andrea Giacomelli, Giulia Burastero, Giordano Madeddu, Eugenia Quiros Roldan, Antonella d'Arminio Monforte, Andrea Antinori, Alessandro Cozzi-Lepri
Summary: This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)