Pharmacokinetics of centhaquin citrate in a rat model

O’Donnell, John M.; O'Donnell, E. Paul; Kumar, E Jeevan; Lavhale, Manish S; Andurkar, Shridhar V.; Gulati, Anil; Scheetz, Marc H.

doi:10.1111/jphp.12498

Cited by 8 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In summary, the pharmacokinetic parameters of centhaquin citrate in dogs have been described with a two‐compartment model. The results of our compartmental analysis are consistent with the results from a previous pharmacokinetic study in healthy rats . Further studies to characterize the pharmacokinetics of centhaquin citrate in humans and to determine optimal dosing schemes are ongoing.…”

Section: Discussionsupporting

confidence: 84%

“…a dog). The pharmacokinetics of centhaquin in a healthy rat model have been reported previously . In this model, centhaquin also exhibited a rapid half‐life and large volume of distribution.…”

Section: Discussionsupporting

confidence: 58%

“…It is important to note that 48 min represents a terminal half‐life, not the half‐life at steady state. Changes in drug concentration for centhaquin in healthy rats were also well explained from a two‐compartment model . In both studies, the first phase of drug concentration decline was prompt and was explained by our model as K e + K cp .…”

Section: Discussionsupporting

confidence: 53%

“…This study is limited by the use of a single species of dogs. Pharmacokinetic studies in rats have been published previously, and pharmacokinetic studies in humans are underway . Pharmacodynamic studies to determine optimal dosing are ongoing.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacokinetics of centhaquin citrate in a dog model

O'Donnell

Kumar³

et al. 2016

Journal of Pharmacy and Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 58%

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics of centhaquin citrate in a dog model

O'Donnell

Kumar³

et al. 2016

Journal of Pharmacy and Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The nonparametric adaptive grid (NPAG) algorithm (29-31) with adaptive gamma implemented within the Pmetrics package (version 1.4.0; Laboratory of Applied Pharmacokinetics and Bioinformatics, Los Angeles, CA) for R (32) was used for all PK model-fitting procedures, as previously described (33)(34)(35)(36). There were 80,021 initial grid points.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats

Rhodes

Prozialeck

Lodise

et al. 2016

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Vancomycin has been associated with acute kidney injury (AKI).A cute kidney injury (AKI) is a major contributor to patient morbidity and mortality in the hospital setting (1, 2). While the etiology of AKI is multifactorial, many cases among hospital patients are related to medication exposure (2). Not surprisingly, the risk of drug-induced AKI is highest among critically ill, hospitalized patients (3), who carry multiple risk factors for the development and progression of AKI. Vancomycin, the antibiotic most frequently administered in the hospital setting (4), has been implicated as a cause of AKI in a number of clinical (5-7) and animal (8-10) studies. Among the clinical studies, the incidence of vancomycin-induced AKI has been associated with higher doses of vancomycin (11, 12), increasing numbers of vancomycin doses (12), and elevated trough concentrations (7, 13).While a number of clinical studies have shown that more intensive vancomycin dosing regimens are associated with an increased risk of AKI, these studies could only suggest an association with kidney injury. As these studies were largely observational in nature, it is difficult to discern if the association was reflective of a true effect or was biased due to confounders. For example, patient confounder factors, such as severity of illness, residence in an intensive care unit, and concurrent receipt of nephrotoxins, may influence the vancomycin exposure-response profile that best predicts clinical AKI.Animal systems are ideally suited to define exposure-response relationships, as they provide flexibility to titrate dosing groups and minimize the influence of external covariates on the observed results. To date, animal models of AKI have confirmed that vancomycin is a nephrotoxin. Dose-ranging studies have revealed that an increase in the vancomycin dose and an increase in the duration of treatment in rats are associated with increases in histopathological damage and elevations in novel urinary biomarkers of AKI (8-10). However, a prospectively derived ex-

show abstract

Investigation of Factors Affecting the Performance of in silico Volume Distribution QSAR Models for Human, Rat, Mouse, Dog & Monkey

Simeon

Montanari

Gleeson

2019

Molecular Informatics

View full text Add to dashboard Cite

Volume of distribution (Vd ss ) is a measure of how effectively a drug molecule is distributed throughout the body. Along with the clearance, it determines the half-life and therefore the drug dosing interval. A number of different pre-clinical approaches are available to predict the Vd ss in human including quantitative structure activity relationship (QSAR) models. Vd ss QSAR models have been reported for human and rat, but not important pre-clinical species including dog, mouse and monkey. In this study, we have generated Vd ss QSAR model on the human and commonly used pre-clinical species, each of which differs in terms of size, chemical diversity and data quality. We discuss the model performance by species, assess the effect the domain of applicability and the relative merits of building chemical series-specific models. In addition, we compare the intrinsic variability of the experimental logVd ss data (~1.2 fold error) to in-vivo interspecies differences (~2 fold error) and in silico based models (~3 fold error). This prompted us to explore whether one species could be used to predict another, particularly where little data for that species is available. i. e. does the expansion in domain of applicability prove beneficial over and above any deterioration due to the use of response values from an alternative species.Keywords: Applicability domain · data mining · quantitative structure-property relationship · volume of distribution [a] S. Simeon

show abstract

Pharmacokinetics of centhaquin citrate in a rat model

Abstract: This is the first report of the pharmacokinetic parameters of centhaquin citrate in a rat model. Centhaquin citrate was found to have a short half-life with a large volume of distribution.

Cited by 8 publications

References 33 publications

Pharmacokinetics of centhaquin citrate in a dog model

Pharmacokinetics of centhaquin citrate in a dog model

Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats

Investigation of Factors Affecting the Performance of in silico Volume Distribution QSAR Models for Human, Rat, Mouse, Dog & Monkey

Contact Info

Product

Resources

About