Comparison of saline vs. blood replenishment after blood sampling in a rat pharmacokinetic study

Kim, Sang-Bum; Kim, Kyu-Sang; Ryu, Heon-Min; Yoon, In‐Soo; Cho, Hyun‐Jong; Chung, Suk‐Jae; Chong, Samuel S.; Kim, Dae‐Duk

doi:10.1007/s40005-018-00420-0

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Rats underwent surgery for cannula implantation into the femoral vein and artery under light ether anaesthesia (Kim et al. 2019 ; Park et al. 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Factors determining the oral absorption and systemic disposition of zeaxanthin in rats: in vitro , in situ , and in vivo evaluations

Seo

Han

Choi

et al. 2022

Pharmaceutical Biology

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Context Zeaxanthin is a yellow‑coloured dietary carotenoid widely recognized as an essential component of the macula. It exerts blue light filtering and antioxidant activities, offering eye health and vision benefits. Objective This study explores the oral absorption and systemic disposition of zeaxanthin from biopharmaceutical and pharmacokinetic perspectives. Materials and methods In vivo intravenous (5 and 10 mg/kg) and intraportal (5 mg/kg) pharmacokinetic studies were performed to determine intrinsic tissue‑blood partition coefficient, elimination pathway, and hepatic clearance, of zeaxanthin in rats. Moreover, in vitro physicochemical property test, in situ closed loop study, in vivo oral pharmacokinetic study (20 and 100 mg/kg), and in vivo lymphatic absorption study (100 mg/kg) were conducted to investigate the gut absorption properties of zeaxanthin and assess the effects of several lipids on the lymphatic absorption of zeaxanthin in rats. Results Zeaxanthin exhibited poor solubility (≤144 ng/mL) and stability (6.0–76.9% of the initial amount remained at 24 h) in simulated gut luminal fluids. Gut absorption of zeaxanthin occurred primarily in the duodenum, but the major fraction (≥84.7%) of the dose remained unabsorbed across the entire gut tract. Considerable fractions of intravenous zeaxanthin accumulated in the liver, lung, and spleen (21.3, 11.7, and 2.0%, respectively). It was found that the liver is the major eliminating organ of zeaxanthin, accounting for 53.5–90.1% of the total clearance process (hepatic extraction ratio of 0.623). Discussion and conclusions To our knowledge, this is the first systematic study to report factors that determine the oral bioavailability and systemic clearance of zeaxanthin.

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“…Rats underwent surgery for cannula implantation into the femoral vein and artery under light ether anaesthesia (Kim et al. 2019 ; Park et al. 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Factors determining the oral absorption and systemic disposition of zeaxanthin in rats: in vitro , in situ , and in vivo evaluations

Seo

Han

Choi

et al. 2022

Pharmaceutical Biology

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“…The rats were fasted overnight before the experiment and anesthetized using an intramuscular injection of zoletil at 20 mg/kg [ 26 ]. The femoral artery and vein were cannulated with a polyethylene tube (Clay Adams, Parsippany, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects

et al. 2021

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Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability.

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“…Drug components including bile acid metabolites were extracted from the tissue using an organic solvent (protein precipitation method with ethanol) [23]. Homogenized supernatant of eyes or plasma (500 μL) were mixed with 50 μL of IS, subjected to the extraction process using ice-cold absolute ethanol, and finally reconstituted in 500 μL of methanol.…”

Section: Methodsmentioning

confidence: 99%

Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration

et al. 2019

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As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.

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Comparison of saline vs. blood replenishment after blood sampling in a rat pharmacokinetic study

Cited by 5 publications

References 27 publications

Factors determining the oral absorption and systemic disposition of zeaxanthin in rats: in vitro , in situ , and in vivo evaluations

Factors determining the oral absorption and systemic disposition of zeaxanthin in rats: in vitro , in situ , and in vivo evaluations

Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects

Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration

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