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Purpose: This study aimed to investigate the effects of 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) on the expression levels of organic cation/carnitine transporter 1 (OCTN1) as well as the pharmacokinetics and biodistribution of ergothioneine, an OCTN1 substrate, in rats., Methods: Rats pretreated with 1,25(OH) 2 D 3 (2.56 nmol/kg/day) for four days were administered ergothioneine (2 mg/kg) intravenously. The expression levels of rat OCTN1 (rOCTN1) in organs were determined using real-time quantitative polymerase chain reaction. Ergothioneine levels in plasma, urine, and organs (with and without intravenous injection of exogenous ergothioneine) were determined using liquid chromatography-tandem mass spectrometry., Results: 1,25(OH) 2 D 3 pretreatment resulted in a significant decrease in rOCTN1 mRNA expression levels in the kidney and brain, a significant increase in basal plasma levels of ergothioneine (from 48 h), and a significant decrease in the tissue-plasma partition coefficient (K p ) in all tissues (except the heart and lungs) and the basal urine levels of ergothioneine. After intravenous administration, the pharmacokinetic profiles of ergothioneine were consistent with the basal levels of endogenous ergothioneine, with an increase in AUC ∞ by 85%, a significant decrease in total clearance by 49%, and a decrease in V ss by 32% in 1,25(OH) 2 D 3 -treated rats. The K p value and urinary recovery of ergothioneine also decreased in the 1,25(OH) 2 D 3 -treated group., Conclusion: This study showed the effects of 1,25(OH) 2 D 3 on the expression and function of rOCTN1 by investigating the interaction between 1,25(OH) 2 D 3 and ergothioneine. Dose adjustment and possible changes in bioavailability should be considered before the co-administration of vitamin D or its active forms and OCTN1 substrates., Supplementary Information: The online version contains supplementary material available at 10.1007/s40005-022-00563-1., (© The Author(s) under exclusive licence to The Korean Society of Pharmaceutical Sciences and Technology 2022.)

Ondansetron hydrochloride (ODS) is a selective 5-hydroxytryptamine type 3 antagonist for nausea and emesis prevention in neoplastic patients. To reduce dosing frequency and side effects and improve patient compliance, a sustained release parenteral formulation of ODS was developed. Microparticles of methylcellulose (MC) and ODS were prepared using the spray-drying method and suspended in oils to form oil suspensions. The formulations were evaluated for residual moisture, drug content, size distribution, DSC, XRD, FTIR, SEM, drug release, and pharmacokinetic studies. The effects of polymers and oils on the drug release were evaluated. MC showed the most prominent sustained release effect among various polymers examined with the optimum MC/ODS ratio of 2:1 (w/w). The particle size of the produced microparticles was in the mean diameter of approximately 3 μm. Physicochemical characterization suggested that ODS existed in an amorphous matrix within the microparticles and interacted with MC via hydrogen bonds. Corn oil was selected as the appropriate oil for suspension due to the sustained release of ODS and the appropriate viscosity. The optimized sustained release formulation of ODS was the corn oil suspension of spray-dried microparticles containing MC and ODS (2:1, w/w). It showed an in vitro drug sustained release up to 120 h, while the oil suspension of ODS without any polymer released the drug within 2 h. Following subcutaneous administration in rats, the optimized formulation could prolong the drug release until 72 h with the enhanced bioavailability in comparison with the ODS solution. The oil suspension of spray-dried microparticles might be an efficient approach for prolongation of the drug effect in the management of nausea and emesis. Graphical abstract.

The objective of this study was to characterize the systemic and tissue kinetics of 2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl) benzofuran (SNU-0039), an inhibitor of β-amyloid protein aggregation, in rats. Simultaneous fitting of the data to polyexponential equations indicated that the systemic clearance and steady state volume of distribution were estimated to be 0.0220 l/min/kg and 2.33 l/kg. The clearance and volume of distribution were not dependent on the intravenous dose, in the range from 5 to 20 mg/kg. The tissue (i.e., the brain, liver, kidneys, heart, spleen, lungs, gut, muscle and adipose tissue) to plasma partition coefficients (K(p)) for SNU-0039 in rats ranged from a low of 0.779 ± 0.314 (muscle) to a high of 5.71 ± 1.66 (liver). The recoveries of DMB were less than 1% of the dose for the renal and biliary excretion, indicative of minor involvements of these pathways in overall elimination. The fraction of bound SNU-0039 to plasma protein was approximately 95.9% and the fraction of SNU-0039 distributed to blood cells was approximately 45.3%. Assuming a flow-limited distribution, the simulated concentration profiles for SNU-0039 in the physiologically based pharmacokinetic model were in reasonable agreement with the observed concentrations in plasma and nine tissues in rats.