The pharmacokinetics of 4-amino-3-chlorophenyl hydrogen sulfate, M-III of resatorvid, in rats and dogs were investigated using radiolabeled M-III ([(14)C]M-III). The elimination half-life of (14)C in the plasma of rats was approximately 1/30 of that of dogs after intravenous dosing of [(14)C]M-III at 0.5 mg/kg to rats and dogs. The in vitro and in vivo plasma protein binding ratios of M-III were relatively high and were the same in both species. The intrinsic clearance (CL(int)) of M-III in rats was much higher than the glomerular filtration rate in rats. Furthermore, the concentration of [(14)C]M-III in the kidney of rats was much higher than that in the plasma. On the contrary, in dogs, the concentration of [(14)C]M-III in the kidney was very much lower than that in the plasma. These results indicated that M-III was effectively taken up into the kidney and was excreted into the urine in rats; however, in dogs, ineffective renal uptake of M-III was presumed. When [(14)C]M-III and probenecid were simultaneously and continually infused intravenously to rats, the CL(int) of M-III decreased with increasing plasma concentrations of probenecid, indicating that kidney uptake of M-III in rats was inhibited by probenecid. It was also thought that uptake by the organic anion transport system(s) in the basolateral membrane is involved in the renal uptake of M-III in rats. The pharmacokinetic differences of M-III between rats and dogs are considered to be mainly caused by the difference in the urinary excretion via the renal distribution processes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1124/dmd.111.043729 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Examination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine.
Cytokine
December 2024
Cancer Research Unit, Sumitomo Pharma Co Ltd, Osaka, Japan. Electronic address:
Toll-like receptors (TLRs) are crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. Because of their strong immunostimulatory activity, TLRs are thought to be a "double-edged sword" for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509.
View Article and Find Full Text PDFLeptospirosis outbreak in Ecuador in 2023: A pilot study for surveillance from a One Health perspective.
One Health
December 2024
One Health Research Group, Universidad de Las Américas, Quito, Ecuador.
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 PDFAdvanced oral breviscapine sustained-release tablets for improved ischemic stroke treatment.
Biomaterials
May 2025
School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Fudan University, Shanghai, 201203, China. Electronic address:
This study aimed to address the challenges associated with the low oral bioavailability and the necessity for frequent dosing of breviscapine (BRE), a mainstream drug in the treatment of cardiovascular and cerebrovascular diseases. The poor solubility and permeability of BRE in the gastrointestinal tract were identified as significant barriers to effective drug absorption, thereby impacting therapeutic efficacy and patient compliance. To enhance the gastrointestinal absorption of BRE, particles loaded with BRE were engineered utilizing Cremophor EL (CrEL), an absorption enhancer, in conjunction with mesoporous silica, a biocompatible drug delivery vector, formulating mesoporous silica particles loaded with BRE and CrEL (BRE-CrEL@SiO).
View Article and Find Full Text PDFEffective, but Safe? Physiologically Based Pharmacokinetic (PBPK)-Modeling-Based Dosing Study of Molnupiravir for Risk Assessment in Pediatric Subpopulations.
ACS Pharmacol Transl Sci
December 2024
Department of Chemical Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
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 PDFInvestigation of the Occurrence of Zoonotic Intestinal Parasites along the Karmanasa River Bank in Lalitpur, Nepal.
Vet Med Sci
January 2025
Department of Zoology, Tri-Chandra Multiple Campus, Tribhuvan University, Kathmandu, Nepal.
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.
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!