A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session19tpjsgo6802viij8vpi0r1237l4dc7a): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated

Filename: models/Detail_model.php

Line Number: 71

Backtrace:

File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos

File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated

Filename: helpers/my_audit_helper.php

Line Number: 8919

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace

File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

Case report of extensive metabolism by aldehyde oxidase in humans: pharmacokinetics and metabolite profile of FK3453 in rats, dogs, and humans. | LitMetric

Case report of extensive metabolism by aldehyde oxidase in humans: pharmacokinetics and metabolite profile of FK3453 in rats, dogs, and humans.

Xenobiotica

Analysis & Pharmacokinetics Research Labs, Discovery Drug Metabolism & Pharmacokinetics, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba City, Ibaraki, Japan.

Published: May 2011

AI Article Synopsis

Article Abstract

We describe the preclinical and clinical pharmacokinetic profiles of FK3453 [6-(2-amino-4-phenylpyrimidin-5-yl)-2-isopropylpyridazin-3(2H)-one] and the mechanism responsible for poor oral exposure of FK3453 in humans. FK3453 showed favourable profiles in preclinical pharmacokinetic studies, including satisfactory absolute bioavailability and total body clearance in animals (30.5%-41.4%, 54.7%-68.2%, and 71.3%-93.4% and 10.8-17.6, 1.9-17.1, and 5.0 mL/min/kg in male rats, female rats, and dogs, respectively), and good metabolic stability in liver microsomes (42.3, 14.5, and 1.1 mL/min/kg in male rats, dogs, and humans, respectively). However, despite these promising preclinical findings, plasma concentrations of FK3453 in humans were extremely low, with the oxidative metabolite of the aminopyrimidine moiety (M4) identified as a major metabolite. Given that aldehyde oxidase (AO) and xanthine oxidase (XO) were presumed to be the enzymes responsible for M4 formation, we investigated the mechanism of M4 formation using human liver subcellular fractions. M4 was detected in the incubation mixture with S9 and cytosol but not with microsomes, and M4 formation was inhibited by AO inhibitors (menadione, isovanillin) but not by cytochrome P-450 inhibitor (1-aminobenzotiazole) or XO inhibitor (allopurinol). These results suggest M4 formation is catalyzed by AO, and therefore, its poor exposure in humans was attributed to extensive AO metabolism.

Download full-text PDF

Source
http://dx.doi.org/10.3109/00498254.2010.549970DOI Listing

Publication Analysis

Top Keywords

rats dogs
12
extensive metabolism
8
aldehyde oxidase
8
dogs humans
8
fk3453 humans
8
ml/min/kg male
8
male rats
8
humans
6
fk3453
5
case report
4

Similar Publications

Leptospirosis is a neglected zoonotic disease that is endemic in tropical regions, including Ecuador. It is caused by spirochetes of the genus , which can infect humans through animal reservoirs such as rats and dogs, or through contact with contaminated water or soil. In March 2023, public health authorities declared a concerning outbreak of leptospirosis in Durán Cantón, located in the Coastal region of Ecuador.

View Article and Find Full Text PDF

Despite the end of COVID-19 pandemic, only intravenous remdesivir was approved for treatment of vulnerable pediatric populations. Molnupiravir is effective against viruses beyond SARS-CoV-2 and is orally administrable without CYP-interaction liabilities but has a burden of potential bone or cartilage toxicity, observed at doses exceeding 500 mg/kg/day in rats. Especially, activity of molnupiravir against viruses, such as Ebola, with high fatality rates and no treatment option warrants the exploration of potentially effective but safe doses for pediatric populations, i.

View Article and Find Full Text PDF

Introduction: Increasing urbanization has particularly affected rivers and their outer edges in cities, including Kathmandu Valley, which encompasses Lalitpur, the nation's third-largest city. This study aims to conduct a parasitological survey to investigate the occurrence of zoonotic intestinal protozoa and helminths along the Karmanasa River bank in central Nepal.

Methods: Faecal samples from openly defaecating animals were collected via non-invasive techniques, and coproscopy was carried out using direct wet mount, concentration and acid-fast staining methods to ensure reliable findings.

View Article and Find Full Text PDF

Establishment and Characterization of Endometrial Organoids from Different Placental Types.

BMB Rep

December 2024

Laboratory of Theriogenology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea; BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul, Republic of Korea; Comparative medicine Disease Research Center, Seoul National University, Seoul 08826, Korea.

Understanding the molecular characteristics and metabolic processes of the mammalian endometrium is crucial for advancing biological research, particularly in veterinary obstetrics and pathology. This study established and analyzed organoids from the endometrial epithelial stem cells of five mammals with different placental types: cows (cotyledonary), dogs and cats (zonary), pigs (diffuse), and rats (discoid). The organoids from these five species were maintained for over 13 passages, successfully frozen-thawed, and confirmed by pathological analysis to retain the characteristics of the original tissues.

View Article and Find Full Text PDF

Mass spectrometry imaging (MSI) was used to investigate and provide insights into observed biliary pathology found in dogs and rats after administration of two different compounds. Both compounds were associated with peribiliary inflammatory infiltrates and proliferation of the bile duct epithelium. However, MSI revealed very different spatial distribution profiles for the two compounds: Compound A showed significant accumulation within the bile duct epithelium with a much higher concentration than in the parenchymal hepatocytes, while Compound T exhibited only a slight increase in the bile duct epithelium compared to parenchymal hepatocytes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!