scholarly journals Tissue Distribution oftrans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Shuaishuai Wang ◽  
Zheng Wang ◽  
Shuo Yang ◽  
Tiemei Yin ◽  
Yaoli Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Aqueous Humor ◽  
High Performance ◽  
Limit Of Detection ◽  
Vitreous Humor ◽  
Average Concentration ◽  
Ocular Tissues ◽  
Suitable Amount ◽  
Pars Plana ◽  
Human Eyes

Purpose.This study was performed to measure the concentration oftrans-resveratrol and its three metabolites in human eyes.Methods.The patients who underwent pars plana vitrectomy for rhegmatogenous retinal detachment were included. The participants were orally giventrans-resveratrol-based supplement (Longevinex®). A suitable amount of conjunctiva, aqueous humor, and vitreous humor were obtained during the operation. High-performance liquid chromatography (HPLC) with mass spectrometry (LC/MS/MS) was used to detect the concentration oftrans-resveratrol and its three metabolites in the various samples.Results.The average concentration of resveratrol in the conjunctiva was 17.19 ± 15.32 nmol/g (mean ± SD). The concentration of resveratrol in the aqueous humor was close to the limit of detection, but its metabolites could be quantified. The concentrations of resveratrol metabolites in the aqueous humor can be detected. In the vitreous humor, the average concentration of resveratrol-3-O-sulfate was 62.95 ± 41.97 nmol/L. The sulfate conjugations of resveratrol were recovered in the conjunctiva, aqueous humor, and vitreous humor.Conclusions.Resveratrol and its three metabolites can be detected in the ocular tissues after oral administration. Although the concentration of parent resveratrol was low in the eyes, its metabolites could be detected and may have a role in the treatment of ocular diseases.

scholarly journals Modeling Approach To Characterize Intraocular Doripenem Pharmacokinetics after Intravenous Administration to Rabbits, with Tentative Extrapolation to Humans

2012 ◽  
Vol 56 (7) ◽  
pp. 3531-3534 ◽  
Author(s):  
Oudy Semoun ◽  
Sandrine Marchand ◽  
Nicolas Grégoire ◽  
Isabelle Lamarche ◽  
Christophe Adier ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
High Performance ◽  
Vitreous Humor ◽  
Time Curve ◽  
Time Profiles ◽  
Modeling Approach ◽  
New Zealand White Rabbits ◽  
Dosing Regimens ◽  
Sampling Times ◽  
Peripheral Elimination

ABSTRACTThe aim of this study was to determine the penetration of doripenem administered intravenously into the rabbit aqueous and vitreous humors. Nineteen New Zealand White rabbits received a 20-mg dose of doripenem intravenously over 60 min. Specimens of aqueous humor, vitreous humor, and blood were obtained 30 min (n= 5), 1 h (n= 5), 2 h (n= 5), and 3 h (n= 4) after the beginning of the infusion and analyzed by high-performance liquid chromatography (HPLC). A pharmacokinetic (PK) model was developed to fit the experimental data. Doripenem concentrations in aqueous humor were lower than those in plasma ultrafiltrates at all sampling times, with an average aqueous humor-to-plasma ultrafiltrate area under the concentration-time curve ratio estimated as 8.3%. A pharmacokinetic model with peripheral elimination described the data adequately and was tentatively used to predict concentration-versus-time profiles and pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients under various dosing regimens. In conclusion, systematically administered doripenem does not seem to be a promising approach for the treatment of intraocular infections, especially since it could not be detected in the vitreous humor. However, this study has provided an opportunity to develop a new PK modeling approach to characterize the intraocular distribution of doripenem administered intravenously to rabbits, with tentative extrapolation to humans.

scholarly journals Cathepsin A activity of normal bovine ocular tissues and pathological human intraocular fluids.

1996 ◽  
Vol 43 (4) ◽  
pp. 687-692 ◽  
Author(s):  
I Obuchowska ◽  
A Stankiewicz ◽  
Z Mariak
Keyword(s):  
Retinal Pigment Epithelium ◽  
Aqueous Humor ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Metastatic Tumor ◽  
Vitreous Humor ◽  
Ph Optimum ◽  
Ocular Tissues ◽  
Intraocular Tumors ◽  
Bovine Ocular Tissues

Cathepsin A activity assayed with N-Cbz-Phe-Ala, N-Cbz-Glu-Tyr and N-Cbz-Glu-Phe as substrates, was measured in fresh corneas, lenses, aqueous humor, vitreous humor and choroid plus retinal pigment epithelium taken from normal bovine eye balls and in human intraocular fluids from the eye balls in various ocular diseases (cataract, glaucoma, diabetes, intraocular tumors). Cathepsin A exhibited a pH optimum at 5.0 and showed the highest specificity towards N-Cbz-Phe-Ala as a substrate. In bovine ocular tissues high cathepsin A activity was found in the choroid plus retinal pigment epithelium and in cornea. The lens and the vitreous humor showed low enzyme activity and the aqueous humor none at all. In the human aqueous humor of the eye with cataract cathepsin A activity was more than three times higher then in the eye with choroid tumor. In human vitreous humor in absolute glaucoma the activity was twice as high as in melanoma and almost three times higher than in the case of lung metastatic tumor. Diabetes in glaucoma increased seven fold cathepsin A activity in the vitreous humor.

ESTIMATION OF THE WITHDRAWAL PERIOD FOR AMOXICILLIN IN POMPANO (TRACHINOTUS BLOCHII) SERUM AND MUSCLE

2015 ◽  
Vol 41 (02) ◽  
pp. 67-72 ◽  
Author(s):  
Chia-Yih Wang ◽  
Shi-Yuan Sheu ◽  
Jiann-Hsiung Wang ◽  
Ming-Huang Chang ◽  
Pay-Heng Chen ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Limit Of Detection ◽  
Reversed Phase ◽  
Multiple Dosing ◽  
Single Oral Administration ◽  
Limit Of Quantitation ◽  
Residue Levels ◽  
Maximum Threshold ◽  
Trachinotus Blochii

Amoxicillin is one of the most popular antibiotics used in aquaculture. To ensure the residue of amoxicillin in the serum and the muscle of pompano (Trachinotus blochii) is below the established tolerance levels; we used reversed phase high-performance liquid chromatography (HPLC) to measure the amoxicillin in pompano after oral administration. The pharmacokinetics of amoxicillin in the serum and the muscle of pompano were established by single oral administration or administrations for five consecutive days at the dose of 40 mg/kg. After different depletion periods, amoxicillin residue was analyzed in both the serum and the muscle fillets by HPLC. The verified concentrations of this method were 0.01 to 10 μg/mL; the limit of detection (LOD) and the limit of quantitation (LOQ) were 0.04 and 0.1 μg/g. The concentration of amoxicillin in the serum of pompano reached the maximum threshold of 7.36 μg/g after 0.5 h depletion in the experiment with a single dose of amoxicillin (40 mg/kg of body weight). In addition, the maximal concentration (1.96 μg/g) of amoxicillin was detected in the muscle 2 h after depletion. Furthermore, the residue levels had decreased below the limit of detection after 48 h and 72 h in the serum and the muscle. Here we also suggested that 5 days of withdrawal were required after the multiple dosing of amoxicillin.

Aqueous Concentration of Tranexamic Acid after 5% and 10% Eyedrop Administration

2009 ◽  
Vol 19 (4) ◽  
pp. 661-666 ◽  
Author(s):  
Hamid R. Jahadi Hosseini ◽  
Hashem Montaseri ◽  
Mohammad R. Khalili ◽  
Shohreh A. Simakani
Keyword(s):  
Side Effects ◽  
Tranexamic Acid ◽  
Aqueous Humor ◽  
High Performance ◽  
Topical Administration ◽  
Average Concentration ◽  
Cataract Operation ◽  
Single Drop ◽  
Limit Of Quantification ◽  
Chromatography Method

Purpose To determine whether topical tranexamic acid can provide acceptable therapeutic concentration in the aqueous humor. Methods A total of 47 patients with cataract as the sole eye disease who have been scheduled for cataract operation received one drop of tranexamic acid 5% solution at various time intervals prior to operation (from 15 minutes to 9 hours). Two patients received 10% solution of the drug. Paracentesis of the anterior chamber was done and the aqueous humor was aspirated in the operation room. The aqueous samples were analyzed using high-performance liquid chromatography method with the limit of quantification around 0.1 μg/mL. Systemic and ocular side effects were evaluated. Results Aqueous concentrations of tranexamic acid was higher than 1.5 μg/mL up to 160 minutes after administration of a single drop of 5% solution of the drug and then declined to an average concentration of 1 μg/mL at 300 minutes which persisted up to 9 hours after administration. In two patients for whom a single drop of 10% tranexamic acid solution was used, aqueous concentrations of 2.72 and 2.90 μg/mL were detected 60 minutes after administration. None of the patients experienced ocular or systemic side effects. Conclusions Topical administration of tranexamic acid is effective in yielding therapeutic intraocular concentrations of drug without any ocular or systemic toxicity.

scholarly journals Intraocular Penetration of Intravenous Micafungin in Inflamed Human Eyes

2013 ◽  
Vol 57 (8) ◽  
pp. 4027-4030 ◽  
Author(s):  
Kiyofumi Mochizuki ◽  
Akira Sawada ◽  
Shinsuke Suemori ◽  
Hideaki Kawakami ◽  
Yoshiaki Niwa ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Antifungal Agents ◽  
Vitreous Humor ◽  
Fungal Disease ◽  
Fungal Diseases ◽  
Intravenous Injections ◽  
Human Eyes ◽  
Intraocular Penetration

ABSTRACTEight eyes of 7 patients with fungal disease received intravenous injections of 150 to 300 mg micafungin, and samples of blood, cornea, retina-choroid, aqueous humor, and vitreous humor were collected. The micafungin levels in all collected samples exceeded the MICs; however, the levels in the vitreous and aqueous humors were lower. Our findings suggest that intravenous micafungin should be given in combination with intravitreal antifungal agents after vitrectomy in severe cases of intraocular fungal diseases.

scholarly journals Quantitative analysis of benzodiazepines in vitreous humor by high-performance liquid chromatography

2016 ◽  
Vol 4 ◽  
pp. 205031211666624 ◽  
Author(s):  
Elham Bazmi ◽  
Behnam Behnoush ◽  
Maryam Akhgari ◽  
Leila Bahmanabadi
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Quantitative Analysis ◽  
High Performance ◽  
Limit Of Detection ◽  
Vitreous Humor ◽  
Liquid Extraction ◽  
Array Detector ◽  
Postmortem Changes ◽  
Liquid Liquid Extraction

Objective: Benzodiazepines are frequently screened drugs in emergency toxicology, drugs of abuse testing, and in forensic cases. As the variations of benzodiazepines concentrations in biological samples during bleeding, postmortem changes, and redistribution could be biasing forensic medicine examinations, hence selecting a suitable sample and a validated accurate method is essential for the quantitative analysis of these main drug categories. The aim of this study was to develop a valid method for the determination of four benzodiazepines (flurazepam, lorazepam, alprazolam, and diazepam) in vitreous humor using liquid–liquid extraction and high-performance liquid chromatography. Methods: Sample preparation was carried out using liquid–liquid extraction with n-hexane: ethyl acetate and subsequent detection by high-performance liquid chromatography method coupled to diode array detector. This method was applied to quantify benzodiazepines in 21 authentic vitreous humor samples. Linear curve for each drug was obtained within the range of 30–3000 ng/mL with coefficient of correlation higher than 0.99. Results: The limit of detection and quantitation were 30 and 100 ng/mL respectively for four drugs. The method showed an appropriate intra- and inter-day precision (coefficient of variation < 10%). Benzodiazepines recoveries were estimated to be over 80%. The method showed high selectivity; no additional peak due to interfering substances in samples was observed. Conclusion: The present method was selective, sensitive, accurate, and precise for the quantitative analysis of benzodiazepines in vitreous humor samples in forensic toxicology laboratory.

Development and Validation of A Reversed Phase-High Performance Liquid Chromatography Method for the Quantitative Estimation of Ramipril Drug Content from Formulated Dosage Form

2016 ◽  
Vol 6 (3) ◽  
Author(s):  
Raju Chandra ◽  
Manisha Pant ◽  
Harchan Singh ◽  
Deepak Kumar ◽  
Ashwani Sanghi
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Active Ingredient ◽  
High Performance ◽  
Limit Of Detection ◽  
Quantitative Estimation ◽  
Reversed Phase ◽  
Uv Detector ◽  
Chromatography Method ◽  
Drug Content

A reliable and reproducible reversed-phase high performance liquid chromatography (RP-HPLC) was developed for the quantitative determination of Remipril drug content from marketed bulk tablets. The active ingredient of Remipril separation achieved with C18 column using the methanol water mobile phase in the ratio of 40:60 (v/v). The active ingredient of the drug content quantify with UV detector at 215 nm. The retention time of Remipril is 5.63 min. A good linearity relation (R2=0.999) was obtained between drug concentration and average peak areas. The limit of detection and limit of quantification of the instrument were calculated 0.03 and 0.09 µg/mL, respectively. The accuracy of the method validation was determined 102.72% by recoveries method.

Development and validation of a LC-MS/MS method for quantification of mobocertinib (TAK-788) in plasma and its application to pharmacokinetic study in rats

2020 ◽  
Vol 23 ◽  
Author(s):  
Bo Li ◽  
Jin Wang ◽  
Xinyao Dou ◽  
Xinjie Zhang ◽  
Xianbei Xue ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Internal Standard ◽  
Selected Reaction Monitoring ◽  
Precipitation Method ◽  
Plasma Samples ◽  
Bioanalytical Method Validation ◽  
Extraction Recovery

Aim and Objective:: An analytical method for the determination of mobocertinib, an investigational tyrosine kinase inhibitor, was developed and optimized by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat plasma. Materials and Methods:: Plasma samples were pretreated by the protein precipitation method with a methanol solution of osimertinib as the internal standard (IS). Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, I.D. 5 μm) column with the temperature maintained at 40 °C. The mobile phase consisted of water (containing 0.1% formic acid) and methanol in a gradient mode at a flow rate of 0.5 mL/min. Mass spectrometric detection was carried out in the selected reaction monitoring (SRM) mode with positive electrospray ionization, and the mass transitions of mobocertinib and osimertinib were m/z 587.01 → 71.88 and m/z 499.80 → 71.94, respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover as per the guidelines for bioanalytical method validation (FDA, 2018). The method was applied to the pharmacokinetic study of mobocertinib in rats by oral gavage at the doses of 2, 6, and 18 mg/kg. A total of 216 plasma samples from 18 rats were analyzed. Results:: It showed good linearity over the range of 1-1000 ng/mL (R2 = 0.9957). The intra-batch accuracy was within 94.65-102.59% and the precision was within 5.49-10.46%. The inter-batch accuracy was within 97.08-102.25% with a precision of 7.54-10.13%. The extraction recovery and matrix factor were acceptable for the bioanalysis of mobocertinib. Additionally, mobocertinib was found to be stable under the detected conditions. Mobocertinib showed linear pharmacokinetic characteristics following oral administration to rats at 2.0-18.0 mg/kg. Conclusion:: The developed and validated method was successfully employed in the pharmacokinetic study in rats following oral administration of mobocertinib at the doses of 2, 6, and 18 mg/kg.

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