Objectives: The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures.
Methods: Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (n = 1000) were performed using NONMEM.
Results: A total of 86 samples of 30 adolescents (12-17 years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0-24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3 m2, where a fixed loading dose (LD) is preferred when BSA ≥ 1.3 m2 and a BSA-based LD is preferred when BSA < 1.3 m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70 mg/day and MD 70 mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1 mg/L. Furthermore, an LD of 70 mg/day and MD of 60 mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1 mg/L in the virtual population.
Conclusions: Our study proposed optimized dosing regimens of caspofungin based on AUC0-24/MIC90 or Ctrough, which may support further individualized treatment.
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http://dx.doi.org/10.1093/jac/dkae276 | DOI Listing |
GEN Biotechnol
December 2023
RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Prime editing has gained significant attention as a next-generation gene editing technology, owing to its unique advantages. However, realizing its potential requires effective delivery strategies. While adeno-associated virus (AAV) has been employed for delivery of prime editors in research settings, it presents inherent limitations related to vector size, ongoing expression, and inability to re-dose patients.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Pharmacy, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Objectives: To assess the pharmacokinetics and pharmacodynamics of imipenem in a retrospective cohort of hospitalized Chinese older patients.
Methods: A population pharmacokinetic (PPK) model was constructed utilizing a nonlinear mixed-effects modeling approach. The final model underwent evaluation through bootstrap resampling and visual predictive checks.
BMC Ophthalmol
January 2025
Department of Vitreoretina, Akhand Jyoti Eye Hospital, Mastichak, Saran, Bihar, India.
Purpose: To compare the anatomical and visual outcomes in eyes with submacular hemorrhage (SMH) treated with a combination of ranibizumab (RBZ) either innovator or biosimilar (Razumab) and intravitreal perfluoropropane gas (CF).
Methods: Treatment naïve neovascular age related macular degeneration (n-AMD) patients with SMH were retrospectively analyzed. Patients received either innovator or biosimilar RBZ (3 loading doses followed by pro re nata regimen) and single injection of intravitreal CF.
Background: Uncertainty about optimal tranexamic acid (TXA) dosage has led to significant practice variation in hip arthroplasty. We aimed to identify the optimal i.v.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Combination therapies using checkpoint inhibitors with immunostimulatory agonists have attracted great attention due to their synergistic therapeutic effects for cancer treatment. However, such combination immunotherapies require specific timing of doses to show sufficient antitumor efficacy. Sequential treatment usually requires multiple administrations of the individual drugs at specific time points, thus increasing the complexity of the drug regimen and compromising patient compliance.
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