Pharmacokinetic Profile of Curcumin and Nanocurcumin in Plasma, Ovary, and Other Tissues

Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 559-564 ◽  
Author(s):  
Wawaimuli Arozal ◽  
Wenny Trias Ramadanty ◽  
Melva Louisa ◽  
Regina Puspa Utami Satyana ◽  
Gaviota Hartono ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Particle Size ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Absorption Process ◽  
Sprague Dawley ◽  
Particle Size Reduction ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Low Solubility

Abstract Background Curcumin is a natural diphenolic compound that is currently being investigated for various cancers, including ovarian cancer. Clinical application of curcumin has been limited due to its low solubility and bioavailability and rapid metabolism and degradation at physiological pH. Particle size is one factor that can affect the absorption process, which thus increases compound solubility and transport across the membrane. This study was conducted to determine the effects of modifying the particle size of curcumin on its pharmacokinetic parameters in blood and other organs. Methods Female Sprague Dawley rats were administered a single oral dose of 500 mg/kg curcumin or nanocurcumin. Blood samples were collected at 10, 15, 30, 45, 75, and 120 min, and ovaries, livers, kidneys, and colons were collected at 180 min. The levels of curcumin in plasma and organs were determined using UPLC-MS/MS, and the pharmacokinetic parameters were evaluated. Results Curcumin levels were detectable and measurable in plasma and organs of rats that were administered curcumin or nanocurcumin. Overall, no statistically significant differences were found in pharmacokinetic parameters between curcumin and nanocurcumin groups in both plasma and organs, except for ovaries. The curcumin levels in plasma, liver, kidney, and colon in the curcumin group were higher than those in the nanocurcumin group. However, curcumin concentrations in ovaries in the nanocurcumin group were 3.6 times higher than those in the curcumin group. Conclusion Particle size reduction of curcumin did not increase the concentration of curcumin in the plasma but increased its distribution in the ovaries.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek
Keyword(s):  
Alcohol Dehydrogenase ◽  
High Performance ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Methanol Poisoning ◽  
Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

Pharmacokinetic Interaction between Asari Radix et Rhizoma and Dried Ginger (Zingiber officinalis) in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Xingxing Zhuang ◽  
Li Zhou ◽  
Renhua Miao ◽  
Shoudong Ni ◽  
Meng Li
Keyword(s):  
High Performance ◽  
Pharmacokinetic Interaction ◽  
Raw Material ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Active Components ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Student’S T ◽  
Student’S T Test

Introduction:: Asari Radix et Rhizoma (ARR) and dried ginger (Zingiber officinalis) (DG) are often used together in drug preparations in traditional Chinese medicine (TCM) to treat respiratory diseases including cold, bronchitis and pneumonia. Previous studies suggested that ARR and/or DG may influence the pharmacokinetics of other herbal components. In the current study, we examined pharmacokinetic interactions between ARR and DG in rats after oral administration. Methods:: We developed a method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to simultaneously measure serum concentrations of two active components each in ARR (L-asarinin and sesamin) and DG (6-gingerol and 6-shogaol). Adult Sprague-Dawley rats were starved overnight, then given ARR extract, DO extract, or a co-decoction of ARR and DG by gastric gavage (6 g raw material per kg body weight; n = 6 per group). Blood samples were collected prior to drug administration and at the following times (h) afterward: 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0. Pharmacokinetic parameters were compared using Student’s t test for independent samples. Results:: A simple, rapid, sensitive analytical method has been developed to detect four bioactive components simultaneously in the ARR-DG herbal pair. Pharmacokinetic parameters including Cmax, Tmax, T1/2 and AUC(0~t) were calculated using the non-compartmental model with the DAS 2.0 pharmacokinetic software. For L-asarinin, Tmax was 2.00 ± 0.00 h in ARR animals and 1.67±0.26 h in ARR-DG animals (P<0.05), T1/2 was 8.58 ± 1.75 h in ARR and 11.93 ± 2.13 h in ARR-DG (P<0.05). For 6-gingerol, Cmax was 350.48 ± 23.85 ng/mL in DG animals and 300.21 ± 20.02 ng/mL in ARR-DG (P<0.01), Tmax was 2.83 ± 0.41 h in DG and 2.17 ± 0.41 h in ARR-DG (P<0.05) and AUC(0~t) was 1.93 ± 0.15 mg/mL•h in ARR and 1.70 ± 0.15 mg/mL•h in ARR-DG (P<0.05). For 6-shogaol, Cmax was 390.28 ± 26.02 ng/mL in DG animals and 455.63 ± 31.01 ng/mL in ARR-DG (P<0.01), Tmax was 2.93 ± 0.10 h in DG and 1.92 ± 0.10 h in ARR-DG (P<0.01), T1/2 was 3.74 ± 0.29 h in DG and 3.28 ± 0.22 h in ARR-DG (P<0.01), and AUC(0~t) was 2.15 ± 0.18 mg/mL•h in DG and 2.73 ± 0.15 mg/mL•h in ARR-DG (P<0.01). Conclusions:: Pharmacokinetic interations between ARR and DG decrease Tmax, increase T1/2 but do not affect overall bioavailability of L-asarinin in ARR. The interactions in ARR-DG decrease Cmax and Tmax but increase T1/2 and AUC(0~t) of 6-gingerol in DG. The interactions increase Cmax and AUC(0~t) but decrease Tmax and T1/2 of 6- shogaol in DG. Interactions in ARR-DG do not affect the pharmacokinetics of sesamin.

Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

2015 ◽  
Vol 5 (2) ◽  
pp. 28-43 ◽  
Author(s):  
Natwaine Sherune Gardner ◽  
Kedon JS Luke ◽  
Andrew O. Wheatley ◽  
Winston G. De La Haye ◽  
Perceval Bahado-Singh ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Nutritional Supplements ◽  
Cytochrome P450 3A4 ◽  
Sprague Dawley ◽  
Plasma Analysis ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Chronic Cocaine ◽  
Metabolite Concentrations ◽  
Plasma Metabolite

The effects that chronic cocaine administration (CCA) have on craving, cocaine metabolite concentrations and cytochrome P450 3A4 isoenzyme (CYP450 3A4) activities in Sprague-Dawley rats following the administration of Salako Nutritional Supplements (SNS) were examined. Five groups of fifty rats were used to assess the effect of the SNS following CCA. Craving was analyzed for each rat using a Conditioned Place Preference protocol. Blood samples were obtained at regular intervals and used to measure cocaine plasma metabolite levels. CYP450 3A4 activity was determined in the liver. Administration of the SNS reduced craving of cocaine significantly, upon discontinuing cocaine in the rats. Blood plasma analysis showing higher benzoylecgonine equilibrium and the CYP450 3A4 levels demonstrated that the SNS possibly aided in the removal of the stored metabolites indicative of increased metabolism of cocaine, enhanced by the Supplements. Results indicate that the SNS formulation reduces craving caused by CCA by increasing the liver CYP450 3A4 activity, resulting in better plasma clearance.

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

scholarly journals Paritaprevir and Ritonavir Liver Concentrations in Rats as Assessed by Different Liver Sampling Techniques

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Charles S. Venuto ◽  
Marianthi Markatou ◽  
Yvonne Woolwine-Cunningham ◽  
Rosemary Furlage ◽  
Andrew J. Ocque ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Needle Aspiration ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Tissue Samples ◽  
Drug Concentrations ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass

ABSTRACT The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA1, FNA3, and FNA5); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C max] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA3 and FNA5, with 18% bias, and FNA1 and FNA3, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.

scholarly journals Bioavailability of Melatonin from Lentil Sprouts and Its Role in the Plasmatic Antioxidant Status in Rats

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 330 ◽  
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Teresa Herrera ◽  
L. Tábata Cayuelas ◽  
Montserrat Dueñas ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Antioxidant Status ◽  
Pharmacokinetic Profile ◽  
Total Phenolic ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Melatonin Administration ◽  
Kaempferol Glycosides ◽  
First Time ◽  
Related Compounds

Melatonin is a multifunctional antioxidant neurohormone found in plant foods such as lentil sprouts. We aim to evaluate the effect of lentil sprout intake on the plasmatic levels of melatonin and metabolically related compounds (plasmatic serotonin and urinary 6-sulfatoxymelatonin), total phenolic compounds, and plasmatic antioxidant status, and compare it with synthetic melatonin. The germination of lentils increases the content of melatonin. However, the phenolic content diminished due to the loss of phenolic acids and flavan-3-ols. The flavonol content remained unaltered, being the main phenolic family in lentil sprouts, primarily composed of kaempferol glycosides. Sprague Dawley rats were used to investigate the pharmacokinetic profile of melatonin after oral administration of a lentil sprout extract and to evaluate plasma and urine melatonin and related biomarkers and antioxidant capacity. Melatonin showed maximum concentration (45.4 pg/mL) 90 min after lentil sprout administration. The plasmatic melatonin levels increased after lentil sprout intake (70%, p < 0.05) with respect to the control, 1.2-fold more than after synthetic melatonin ingestion. These increments correlated with urinary 6-sulfatoxymelatonin content (p < 0.05), a key biomarker of plasmatic melatonin. Nonetheless, the phenolic compound content did not exhibit any significant variation. Plasmatic antioxidant status increased in the antioxidant capacity upon both lentil sprout and synthetic melatonin administration. For the first time, we investigated the bioavailability of melatonin from lentil sprouts and its role in plasmatic antioxidant status. We concluded that their intake could increase melatonin plasmatic concentration and attenuate plasmatic oxidative stress.

scholarly journals Studies on the Toxicity and Distribution of Indium Compounds According to Particle Size in Sprague-Dawley Rats

2014 ◽  
Vol 30 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Cheol Hong Lim ◽  
Jeong-Hee Han ◽  
Hae-Won Cho ◽  
Mingu Kang
Keyword(s):  
Particle Size ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Indium Compounds

Pharmacokinetics of BAX 826, a Polysialylated Full-Length rFVIII, in Hemophilia a Mice, Rats, and Cynomolgus Monkeys

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1073-1073 ◽  
Author(s):  
Alexandra Schiviz ◽  
Gerald Hoebarth ◽  
Martin Wolfsegger ◽  
Paolo Rossato ◽  
Alfred Weber ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Geometric Mean ◽  
Pharmacokinetic Profile ◽  
Activity Level ◽  
Full Length ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Target Dose ◽  
Cynomolgus Monkeys ◽  
Fviii Activity

Abstract Factor VIII (FVIII) is a critical component of the intrinsic coagulation pathway. Plasma-derived or recombinant (r) FVIII concentrates are used in patients with hemophilia A to provide a FVIII level sufficient to treat and prevent bleeding episodes. Prophylactic FVIII levels can only be maintained by administering several infusions per week. Extended FVIII circulation times would reduce the frequency of infusions, increase patient compliance, reduce the number of bleeds, and offer the possibility to achieve higher trough levels of FVIII. Prolonged circulation can be achieved by modifying the FVIII molecule with hydrophilic polymers, for example with polysialic acid (PSA). BAX 826, Baxalta's polysialylated FVIII is based on ADVATE, a full length recombinant FVIII molecule with an established extensive safety and efficacy profile. The aim of the presented studies was to assess the pharmacokinetic profile of BAX 826 in hemophilia A mice, wild-type rats, and cynomolgus monkeys. Unmodified rFVIII (ADVATE) was used as the reference compound. Test and reference compounds were administered at the same dose. Hemophilia A mice and Sprague Dawley rats were intravenously injected with BAX 826 at a target dose of 200 IU/kg rFVIII, and blood was sampled pre-dose and 5 min to 48 h after administration. Cynomolgus monkeys received a target dose of 350 IU/kg rFVIII and blood sampled 5 min to 120 h after administration. Citrated plasma was prepared and analyzed for FVIII activity (chromogenic), FVIII antigen (ELISA), and PSA-rFVIII concentration. The primary endpoint was area under the curve from administration time to the last quantifiable time point (AUC0-tlast). Mean residence time (MRT) and systemic clearance (CLs) were also assessed. Unless stated otherwise, results for FVIII activity (mice, monkeys) and FVIII antigen (rats) are presented. In mice, the AUC0-tlast for BAX 826 was 20.6 h*IU/mL, which was 2.4 times larger than for ADVATE (8.71 h*IU/mL); MRT was 10.6 h for BAX 826 and 5.8 h for ADVATE. Clearance was lower for BAX 826 (9.4 vs. 22.3 mL/h/kg). In rats, the AUC0-tlast for BAX 826 was 18.0 h*IU/mL, which was 1.8 times larger than for ADVATE (9.9 h*IU/mL). MRT was 12.5 h for BAX 826 and 4.0 h for ADVATE, and CLs was 5.3 and 28.1 mL/h/kg. In monkeys, the geometric mean of AUC0-tlast was 189.0 h*IU/mL for BAX 826 and 39.6 h*IU/mL for ADVATE. MRT was 23.4 and 10.1 h, and CLs was 2.25 and 6.72 mL/h/kg for BAX 826 and ADVATE, respectively. In monkeys, a baseline FVIII activity level was detected and adequately taken into account in calculating pharmacokinetic parameters. Nevertheless, to better follow the pharmacokinetic profile of BAX 826, the polysialylated rFVIII concentration was also assessed using a PSA specific assay. PSA-FVIII was measured in all animals after administration of BAX 826. In summary, pharmacokinetics studies in three animal species provided evidence that modification of ADVATE with PSA increases circulation time and exposure compared with the unmodified protein. Disclosures Schiviz: Baxalta Innovations GmbH: Employment. Hoebarth:Baxalta Innovations GmbH: Employment. Wolfsegger:Baxalta Innovations GmbH: Employment. Rossato:Baxalta Innovations GmbH: Employment. Weber:Baxalta Innovations GmbH: Employment. Gritsch:Baxalta Innovations GmbH: Employment. Rottensteiner:Baxalta Innovations GmbH: Employment. Turecek:Baxalta Innovations GmbH: Employment. Scheiflinger:Baxalta Innovations GmbH: Employment. Hoellriegl:Baxalta Innovations GmbH: Employment. Putz:Baxalta Innovations GmbH: Employment.

scholarly journals Orange Juice and Its Component, Hesperidin, Decrease the Expression of Multidrug Resistance-Associated Protein 2 in Rat Small Intestine and Liver

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Minoru Watanabe ◽  
Naoki Matsumoto ◽  
Yuko Takeba ◽  
Toshio Kumai ◽  
Masami Tanaka ◽  
...  
Keyword(s):  
Small Intestine ◽  
Multidrug Resistance ◽  
Orange Juice ◽  
Tap Water ◽  
Pharmacokinetic Parameters ◽  
Mrna Levels ◽  
Rat Small Intestine ◽  
Sprague Dawley ◽  
Water Ingestion ◽  
Sprague Dawley Rats

We investigated the effects of orange juice (OJ) or hesperidin, a component of OJ, on the pharmacokinetics of pravastatin (PRV) and the expression of both protein and mRNA of multidrug resistance-associated protein 2 (Mrp2) in the rat small intestine and liver. Eight-week-old male Sprague-Dawley rats were used in this study. OJ or a 0.079% hesperidin suspension was administered orally for 2 days. Tap water was given as a control. A single dose of PRV at 100 mg/kg p.o. was administered after 2 days of OJ, hesperidin, or tap water ingestion. The AUC, , andt1/2values of PRV were significantly increased in OJ group. Mrp2 protein and mRNA levels in the small intestine and liver, respectively, were significantly decreased after the ingestion of OJ. The same results were obtained with hesperidin. These results suggest that the changes in PRV pharmacokinetic parameters and the decrease in Mrp2 expression caused by OJ are due to hesperidin in the juice.

Pharmacokinetics of All-trans Retinoyl beta-Glucuronide in Rats following Intraperitoneal and Oral Administration

2003 ◽  
Vol 73 (4) ◽  
pp. 251-257 ◽  
Author(s):  
Romans ◽  
Barua ◽  
Olson
Keyword(s):  
High Performance Liquid Chromatography ◽  
Single Dose ◽  
High Performance ◽  
Corn Oil ◽  
Major Product ◽  
Plasma Samples ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Plasma Retinol

The purpose of this study was to examine the pharmacokinetics of a single dose (6.3 mumol, 3 mg) of all-trans retinoyl beta-glucuronide (RAG), when given either orally in corn oil or by intraperitoneal (IP) injection in dimethylsulfoxide (DMSO) to adult Sprague-Dawley rats. Following dosing, serial blood samples were collected at various times up to 48 hours from each rat via saphenous vein puncture. Retinoids were extracted from plasma samples and analyzed by high-performance liquid chromatography. In the plasma of IP-dosed rats (n = 6), a derivative of RAG, tentatively identified as the lactone of RAG (RAGL), was the major product found. RAGL persisted in the plasma for up to 48 hours. Much smaller concentrations of RAG and of retinoic acid (RA) were also present in the plasma at two to four hours, but generally not thereafter. In orally dosed rats (n = 6), neither RAG nor its products, except for occasional traces of the lactone, were detected. Plasma retinol levels decreased in both IP-injected and orally treated rats, the decrease being significant in orally dosed rats.

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