External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

Background: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation.

Comparison of cisplatin-induced nephrotoxicity between single-dose and split-dose administration to rats.

To prevent cisplatin (CDDP)-induced nephrotoxicity, co-treatment with massive hydration is essential for its clinical use. However, some patients are ineligible for this treatment. For such patients, a split dose of CDDP has been suggested as an alternative strategy.

Effects of Probenecid on Hepatic and Renal Disposition of Hexadecanedioate, an Endogenous Substrate of Organic Anion Transporting Polypeptide 1B in Rats.

The aim of the present study was to investigate changes in plasma concentrations and tissue distribution of endogenous substrates of organic anion transporting polypeptide (OATP) 1B, hexadecanedioate (HDA), octadecanedioate (ODA), tetradecanedioate (TDA), and coproporphyrin-III, induced by its weak inhibitor, probenecid (PBD), in rats. PBD increased the plasma concentrations of these four compounds regardless of bile duct cannulation, whereas liver-to-plasma (K) and kidney-to-plasma concentration ratios of HDA and TDA were reduced. Similar effects of PBD on plasma concentrations and K of HDA, ODA, and TDA were observed in kidney-ligated rats, suggesting a minor contribution of renal disposition to the overall distribution of these three compounds.

Evaluation of Alteration in Hepatic and Intestinal BCRP Function In Vivo from ABCG2 c.421C>A Polymorphism Based on PBPK Analysis of Rosuvastatin.

Polymorphism c.421C>A in the gene is thought to reduce the activity of breast cancer resistance protein (BCRP), a xenobiotic transporter, although it is not clear which organ(s) contributes to the polymorphism-associated pharmacokinetic change. The aim of the present study was to estimate quantitatively the influence of c.

L503F variant of carnitine/organic cation transporter 1 efficiently transports metformin and other biguanides.

Objectives: Carnitine/organic cation transporter 1 (OCTN1) is involved in gastrointestinal absorption and mitochondrial toxicity of biguanides in rodents, but its pharmacokinetic roles in humans are largely unknown. The purpose of this study was to clarify the transport activities of two major OCTN1 variants, L503F and I306T, for gabapentin and three biguanide drugs, metformin, buformin and phenformin.

Methods: HEK293 cells were transfected with OCTN1 gene, its variants, or vector alone, and the uptake and cytotoxicity of each drug were examined.

Localization of Xenobiotic Transporter OCTN1/SLC22A4 in Hepatic Stellate Cells and Its Protective Role in Liver Fibrosis.

Xenobiotic transporters play key roles in disposition of certain therapeutic agents, although limited information is available on their roles other than pharmacokinetic issues. Here, suppressive effect of multispecific organic cation transporter OCTN1/SLC22A4 on liver fibrosis was proposed in liver injury models. After injection of hepatotoxins such as dimethylnitrosamine (DMN) or concanavalin A, hepatic fibrosis, and oxidative stress, evaluated in terms of Sirius red and 4-hydroxy-2-nonenal staining, respectively, were more severe in liver of octn1/slc22a4 gene knockout (octn1(-/-)) mice than that in wild-type mice.