Publications by authors named "Walter M Yamada"
Unlabelled: Patients are often switched between generic formulations of the same drug, but in some cases generic interchangeability is questioned. For generic drugs to be approved, bioequivalence with the innovator drug should be demonstrated, but evidence of bioequivalence is not required in the intended patient population or relative to other approved generics.
Aim: We aim to identify pathophysiological pharmacokinetic subpopulations for whom there is a difference in comparative bioavailability compared to a healthy population.
Article Synopsis
- This study compares parametric and nonparametric population pharmacokinetic modeling of the antibiotic imipenem in critically ill patients to enhance dosing effectiveness.* -
- While both modeling approaches showed adequate predictive performance for patients with eGFRs (estimated Glomerular Filtration Rate) ≥ 78 mL/min, they were less reliable for patients with lower eGFRs.* -
- Simulations revealed that while 50% of the Probability of Target Attainment (PTA) results were similar between models, differences arose due to higher variability in the nonparametric model, highlighting the need for further investigation on clinical implications.*
Mycobacterium tuberculosis metabolic state affects the response to therapy. Quantifying the effect of antimicrobials in the acid and nonreplicating metabolic phases of M. tuberculosis growth will help to optimize therapy for tuberculosis.
View Article and Find Full Text PDFPopulation pharmacokinetic (PK) modeling has become a cornerstone of drug development and optimal patient dosing. This approach offers great benefits for datasets with sparse sampling, such as in pediatric patients, and can describe between-patient variability. While most current algorithms assume normal or log-normal distributions for PK parameters, we present a mathematically consistent nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions without any assumption about the shape of the distribution.
View Article and Find Full Text PDFBuilding Optimal Three-Drug Combination Chemotherapy Regimens.
Antimicrob Agents Chemother
October 2020
Multidrug therapy is often required. Examples include antiviral therapy, nosocomial infections, and, most commonly, anti- therapy. Our laboratory previously identified a mathematical approach to identify 2-drug regimens with a synergistic or additive interaction using a full factorial study design.
View Article and Find Full Text PDFArticle Synopsis
- The study explores population pharmacokinetic (popPK) models for the antibiotic imipenem in critically ill patients to determine the differences between parametric and nonparametric modeling approaches.
- Both model types identified similar covariates for dosing strategies, but the nonparametric model exhibited higher between-subject variability (BSV) in pharmacokinetic parameters.
- The findings suggest that while both models are valid, the higher BSV in the nonparametric model could impact dosing simulations, warranting further investigation.
Article Synopsis
- Substitution of generic drugs for originator drugs is permitted if bioequivalence is shown, but individual patients may react differently.* -
- The research aims to explore if different pharmacokinetic subpopulations exist when people use bioequivalent drug formulations.* -
- A two-compartment pharmacokinetic model for gabapentin was developed using data from a bioavailability study, confirming that absorption and clearance vary by formulation and are influenced by renal function.*
Article Synopsis
- Nonparametric population modeling algorithms are more effective than parametric methods for identifying distinct pharmacokinetic and pharmacodynamic groups and outliers in study populations.
- The researchers developed "Pmetrics," a new software package that enhances previous tools for population modeling and simulation of drug behaviors.
- Pmetrics effectively identified true distributions and outliers in simulations, showcasing its superiority over parametric methods, especially in cases of bimodal characteristics in elimination rates.
Nonlinear dynamic neural network for text-independent speaker identification using information theoretic learning technology.
Conf Proc IEEE Eng Med Biol Soc
March 2008
Article Synopsis
- The paper introduces a new design for a nonlinear dynamic neural network aimed at text-independent speaker recognition without needing precise voice signatures.
- It employs a high-order synaptic neural model that incorporates memory of past inputs to enhance the relationship between input and output neurons.
- The study focuses on improving recognition accuracy and increasing the uniqueness of voice profiles between different speakers.
Article Synopsis
- The study focuses on the use of the first-order Wiener kernel to assess excitation and timing in cochlear axons with low characteristic frequencies (CF).
- For high-CF axons, the highest-ranking eigenvector from the second-order Wiener kernel can effectively represent the first-order kernel, while mid-CF axons display similar functions for both kernels.
- The researchers analyze gerbil cochlear-nerve axons across a frequency range from 700 Hz to 14 kHz, using eigen decomposition to differentiate between excitatory and suppressive effects and to fine-tune the timing of these effects.
Article Synopsis
- The second-order Wiener kernel is used to analyze excitation, adaptation, and suppression in auditory axons by visualizing data with two-dimensional graphs for excitation and inhibition.
- Patterns like checkerboards and parallel diagonal lines indicate different non-linear response types in auditory units, specifically low-to-mid frequencies.
- The study includes interpretations of these patterns based on recordings from amphibian-papillar units in American bullfrogs, deriving the kernel through reverse correlation with a broad-band white-noise stimulus.