scholarly journals Pharmacokinetic/pharmacodynamic modeling and simulation of dotinurad, a novel uricosuric agent, in healthy volunteers

2019 ◽  
Vol 7 (6) ◽  
Author(s):  
Keisuke Motoki ◽  
Takako Igarashi ◽  
Koichi Omura ◽  
Hiroshi Nakatani ◽  
Takashi Iwanaga ◽  
...  
Keyword(s):  
Modeling And Simulation ◽  
Healthy Volunteers ◽  
Pharmacodynamic Modeling ◽  
Uricosuric Agent

Pharmacokinetic/Pharmacodynamic Modeling of Psychomotor Impairment Induced by Oral Clonazepam in Healthy Volunteers

2009 ◽  
Vol 31 (5) ◽  
pp. 566-574 ◽  
Author(s):  
Fábio Monteiro dos Santos ◽  
José Carlos Saraiva Gonçalves ◽  
Ricardo Caminha ◽  
Gabriel Estolano da Silveira ◽  
Claúdia Silvana de Miranda Neves ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Pharmacodynamic Modeling ◽  
Psychomotor Impairment

Pharmacokinetic-pharmacodynamic modeling of the effects of ivabradine, a direct sinus node inhibitor, on heart rate in healthy volunteers*

1998 ◽  
Vol 64 (2) ◽  
pp. 192-203 ◽  
Author(s):  
Isabelle Ragueneau ◽  
Christian Laveille ◽  
Roeline Jochemsen ◽  
Guillemette Resplandy ◽  
Christian Funck-Brentano ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Volunteers ◽  
Sinus Node ◽  
Pharmacodynamic Modeling

scholarly journals Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis of CTB-001, Recently Developed Bivalirudin

2017 ◽  
Vol 39 (8) ◽  
pp. e54
Author(s):  
S. Han ◽  
H. Youn Choi ◽  
Y. Han Kim ◽  
W. Joo Kim ◽  
K.-S. Bae ◽  
...  
Keyword(s):  
Modeling And Simulation ◽  
Simulation Analysis ◽  
Pharmacodynamic Modeling

Maxacalcitol Pharmacokinetic–Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis

Drug Research ◽  
2021 ◽  
Author(s):  
Mizuki Fukazawa-Shinotsuka ◽  
Tomohisa Saito ◽  
Masaichi Abe ◽  
Satofumi Iida ◽  
I-Ting Wang ◽  
...  
Keyword(s):  
Clinical Study ◽  
Modeling And Simulation ◽  
Secondary Hyperparathyroidism ◽  
Compartment Model ◽  
Japanese Patients ◽  
Pharmacodynamic Modeling ◽  
Maintenance Hemodialysis ◽  
Population Pharmacokinetic ◽  
Limit Of Quantification ◽  
Clinical Pharmacology Study

Abstract Background Maxacalcitol was approved in Taiwan in 2018 as the first active vitamin D3 injection for secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis. However, no data from any clinical study with maxacalcitol in Taiwanese patients is available. Objectives This analysis aimed to evaluate the profiles of parathyroid hormone (PTH) and calcium (Ca) concentrations in Taiwanese SHPT patients on hemodialysis and maxacalcitol. Methods We developed population pharmacokinetic (PK) and pharmacodynamic (PD) models using a modeling and simulation approach. The data for these analyses were obtained from two studies: a clinical pharmacology study in Japanese patients and an ethnic comparison study in healthy Japanese and -Taiwanese volunteers. We then conducted a simulation study with a PK-PD model comprising the PK and PD models developed here. Results Serum maxacalcitol concentration profile was modeled using a two-compartment model that took into consideration the distribution of concentrations below the lower limit of quantification. An ethnic difference in clearance was included in the PK model as a covariate. A PD model that used a PTH/Ca feedback loop best described the observed data. There were no significant differences in Ca or PTH concentrations between Taiwanese and Japanese based on the simulation results from our PK-PD model, even though maxacalcitol exposure was approximately 40% higher in Taiwanese than in Japanese. Conclusions On the basis of these population PK and PD analyses and the clinical study conducted in Japan, there is no clinically relevant difference between Taiwanese and Japanese in terms of serum Ca or PTH levels.

Phase 1 Clinical Trials of Small Molecules: Evolution and State of the Art

2021 ◽  
Vol 16 ◽  
Author(s):  
John J. Sramek ◽  
Michael F. Murphy ◽  
Sherilyn Adcock ◽  
Jeffrey G. Stark ◽  
Neal R. Cutler
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Healthy Volunteers ◽  
Small Molecules ◽  
Phase 1 ◽  
Dose Range ◽  
Pharmacodynamic Modeling ◽  
Inpatient Setting ◽  
Conducting Phase ◽  
Safe Dose

Background: Phase 1 studies comprise the first exposure of a promising new chemical entity in healthy volunteers or, when appropriate, in patients. To assure a solid foundation for subsequent drug development, this first step must carefully assess the safety and tolerance of a new compound, and often provide some indication of potential effect, so that a safe dose or dose range can be confidently selected for the initial Phase 2 efficacy study in the target patient population. Methods: This review was based on a literature search using both Google Scholar and PubMed, dated back to 1970, using search terms including “healthy volunteers”, “Phase 1”, and “normal volunteers” , and also based on the authors’ own experience conducting Phase 1 clinical trials. This paper reviews the history of Phase 1 studies of small molecules and their rapid evolution, focusing on the critical single and multiple dose studies, their designs, methodology, use of pharmacokinetic and pharmacodynamic modeling, application of potentially helpful biomarkers, study stopping criteria, and novel study designs. Results: We advocate for determining the safe dose range of a new compound by conducting careful dose escalation in a well-staffed inpatient setting, defining the maximally tolerated dose (MTD) by reaching the minimally intolerated dose (MID). The dose immediately below the MID is then defined as the MTD. This is best accomplished by using appropriately screened patients for the target indication, as patients in many CNS indications often tolerate doses differently than healthy non-patients. Biomarkers for safety and pharmacodynamic measures can also assist in further defining a safe and potentially effective dose range for subsequent clinical trial phases. Conclusion: Phase 1 studies can yield critical insights to the pharmacology of a new compound in man and offer perhaps the only development period in which the dose range can be safely and thoroughly explored. Phase 1 studies often contain multiple endpoint objectives, the reconciliation of which can present a dilemma for drug developers and study investigators alike, but which can crucially determine whether a compound can survive to the next step in the drug development process.

Pharmacokinetic/pharmacodynamic modeling and simulation to determine effective dosage regimens for doripenem

2010 ◽  
Vol 99 (5) ◽  
pp. 2483-2491 ◽  
Author(s):  
Takayuki Katsube ◽  
Yoshitaka Yano ◽  
Toshihiro Wajima ◽  
Yoshinori Yamano ◽  
Mikihisa Takano
Keyword(s):  
Modeling And Simulation ◽  
Effective Dosage ◽  
Pharmacodynamic Modeling ◽  
Dosage Regimens
Sign in / Sign up

Export Citation Format

Share Document