Influence of Liver Intoxication by Carbon Tetrachloride or D-Galactosamine on Absorption of Fluorescein Isothiocyanate-Dextran-10 and Other Marker Compounds with Different Molecular Weights from the Rat Liver Surface

Miyamoto, Hirotaka; Tsuda, Kayoko; Honda, Tominori; Tokunaga, Ayako; Fumoto, Shintaro; Nishida, Koyo

doi:10.1248/bpb.b19-00686

Cited by 2 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5) Controlled drug retention around the organ surface has been emphasized to improve drug availability to the diseased region. 6,7) Furthermore, it is impossible to apply a drug to the organ surface by employing an administration device of the diffusion cell in the clinical therapy. Different types of drug delivery system formulations, such as gels, 8) patch, 8) and implant 9) have been developed of anticancer drugs, like 5-fluorouracil (5-FU).…”

Section: Introductionmentioning

confidence: 99%

Development of a Two-Layered Sheet Formulation of 5-Fluorouracil for Application to Rat’s Livers to Ensure Controlled Release and Local Drug Disposition

Akagi

Kariya

Hamasaki

et al. 2023

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

This study aimed to develop a new and effective application form for the liver surface. We designed a two-layered sheet for the controlled release and local disposition of the anticancer drug, 5-fluorouracil (5-FU), without leakage into the peritoneal cavity. We employed poly(lactic-co-glycolic acid) (PLGA) and hydroxypropyl cellulose (HPC) to form two-layered sheets by attaching a cover sheet and a drug-containing sheet. The prepared two-layered sheets released 5-FU constantly for up to 14 d without any significant leakage from the cover side in vitro. Furthermore, we have applied sheets containing 5-FU to the rat liver surface in vivo. Notably, 5-FU could be detected in the liver attachment region even 28 d after application. The distribution ratio of 5-FU in the attachment region compared to the other liver lobes varied among the sheet formulations with different additive HPC compositions. The area under the liver concentration-time curve (AUC) of 5-FU in the attachment region from 0 to 28 d was the highest in the case of HPC 2% (w/w). This is probably due to the enhanced 5-FU released amount and controlled absorption rate from the liver surface by released HPC. No critical toxic effects were evident by the application of the two-layered sheets from the body weight change and alanine aminotransferase/aspartate aminotransferase (ALT/AST) activities. Consequently, the possible advantage of the two-layered sheets for prolonged retention of a drug in a specific region in the liver was clarified.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of a Two-Layered Sheet Formulation of 5-Fluorouracil for Application to Rat’s Livers to Ensure Controlled Release and Local Drug Disposition

Akagi

Kariya

Hamasaki

et al. 2023

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

show abstract

Optimization of Drug Administration in Special Populations Focusing on Drug Distribution

Miyamoto

2024

YAKUGAKU ZASSHI

View full text Add to dashboard Cite

Patients with special backgrounds such as organ dysfunction, elderly individuals, children, and pregnant or nursing women in whom the pharmacokinetics of an agent are expected to differ from those observed in the general patient population, are referred to as special populations. Administration of drug therapy to these patients warrants close attention to and knowledge of altered pharmacokinetics to design appropriate personalized dosing regimens. In this study, we investigated the effects of hypothermia and renal impairment on drug pharmacokinetics, focusing on tissue distribution. Analysis of the effects of hypothermia on local liver kinetics of drugs revealed decreased activity of drug-metabolizing enzymes and transporters. Furthermore, we investigated in vivo drug pharmacokinetics and observed that blood drug concentrations increased with a decrease in the body temperature. However, the tissue concentration of midazolam (MDZ) remained unchanged even with a decrease in body temperature, which indicates reduced tissue transfer of MDZ. With regard to the effect of renal impairment, blood concentration of MDZ decreased in patients with acute renal failure and increased in those with chronic renal failure. However, MDZ clearance was decreased in patients with chronic renal failure owing to decreased expression of hepatic metabolic enzymes and reduced hepatic blood flow. This study highlights that tissue translocation of drugs differs across special populations and that optimization of drug administration based on the prediction of tissue concentrations is important.

show abstract

Influence of Liver Intoxication by Carbon Tetrachloride or D-Galactosamine on Absorption of Fluorescein Isothiocyanate-Dextran-10 and Other Marker Compounds with Different Molecular Weights from the Rat Liver Surface

Cited by 2 publications

References 16 publications

Development of a Two-Layered Sheet Formulation of 5-Fluorouracil for Application to Rat’s Livers to Ensure Controlled Release and Local Drug Disposition

Development of a Two-Layered Sheet Formulation of 5-Fluorouracil for Application to Rat’s Livers to Ensure Controlled Release and Local Drug Disposition

Optimization of Drug Administration in Special Populations Focusing on Drug Distribution

Contact Info

Product

Resources

About