scholarly journals Development of a Novel Nano­emulsion Formulation to Improve Intestinal Absorption of Cannabidiol

2019 ◽  
Vol 2 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Yukako Nakano ◽  
Masataka Tajima ◽  
Erika Sugiyama ◽  
Vilasinee Hirunpanich Sato ◽  
Hitoshi Sato
Keyword(s):  
Oral Administration ◽  
Micelle Formation ◽  
Bile Secretion ◽  
Tween 20 ◽  
Pharmacokinetic Parameters ◽  
The Novel ◽  
Onset Of Action ◽  
Vitamin E Acetate ◽  
Pharmacokinetic Profiles ◽  
Oil Formulation

Background: Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated. Methods: The CBD-NE formulation developed in this study consisted of vitamin E acetate, ethanol, Tween-20, and distilled water (1.7/3.8/70/24.5, w/w%). A CBD oil formulation (CBD oil, control) 100 mg/kg or CBD-NE 50 mg/kg was orally administered to rats, and the blood samples were collected over time. Moreover, the CBD oil or CBD-NE was orally administered to bile-fistulated rats, and the pharmacokinetic profiles of CBD were also evaluated. CBD concentrations in plasma were measured using LC-MS/MS. Results: The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean Tmax of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, p < 0.001) and AUC0–∞/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC0–∞/dose and Cmax/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (p < 0.05 and p < 0.01), respectively, in bile-fistulated rats compared with the untreated rats. In contrast, all pharmacokinetic parameters after oral administration of CBD-NE were not significantly different between the untreated and bile-fistulated rats. Therefore, these results demonstrated that conventional CBD oil formulation but not CBD-NE requires bile-mediated micelle formation. Conclusions: The novel NE formulation developed in this study successfully improved the absorption of CBD regardless of bile secretion. The newly developed oral CBD-NE preparation could be useful to achieve a more stable and quicker onset of action by CBD.

scholarly journals CHARACTERIZATION OF PHARMACOKINETICS OF 2-((3-(CHLOROMETHYL)BENZOYL)OXY) BENZOIC ACID IN RATS BY USING HPLC-DAD METHOD

2019 ◽  
pp. 279-283
Author(s):  
Caroline ◽  
Nathania Sie ◽  
Kuncoro Foe ◽  
Senny Yesery Esar ◽  
Maria Anabella Jessica
Keyword(s):  
Benzoic Acid ◽  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartment Model ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Log P ◽  
Potential Candidate ◽  
Onset Of Action ◽  
Fasting Period

Objective: A new compound of salicylic acid derivative, namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3CBB), was synthesized to find a compound exhibiting higher analgesic activity and smaller ulcer irritation than acetylsalicylic acid (ASA). Therefore, this study aimed to investigate the pharmacokinetics of this new compound in rats, following a single dose oral administration of 3CBB (45 mg/kg BW). Methods: Plasma samples of 9 healthy rats were collected before and up to 3 h after its oral administration, following an 18 h fasting period. Plasma concentrations of 3CBB were determined using a validated HPLC-DAD assay. Pharmacokinetic parameters were determined using the compartment model technique. All experiments were carried out in triplicate. Results: The pharmacokinetic parameters of 3CBB obtained were as follows: Tmax= 28.9±1.1 min, Cmax = 0.57±0.02 µg/ml, AUCtotal = 66.3±1.0 µg min/ml, Kel = 0.018±0.002 min-1, and T1/2el = 39.4±3.9 min. The long elimination half-life and low Cmax indicated that 3CBB was extensively distributed in the deep and very deep tissues. This confirmed the unique and special characteristics of a highly lipophilic compound like 3CBB (log P = 3.73). Conclusion: 3CBB demonstrated a slower onset of action and longer elimination time from the body compared to ASA. Thus this new compound is a potential candidate to be developed as a new drug.

Comparative pharmacokinetic study of hesperetin after oral administration in normal and hyperuricemia rats by UPLC-MS/MS

2020 ◽  
Vol 15 ◽  
Author(s):  
Kexin Li ◽  
Li Wei ◽  
Zhigang Han ◽  
Huarong Xiong ◽  
Fengmei Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Specific Method ◽  
Sprague Dawley ◽  
Post Dose ◽  
Pharmacokinetic Profiles ◽  
Group A ◽  
Tandem Mass Spectrometric ◽  
Group B

Backgrounds: Hesperetin has antihyperuricemia activity, and the pharmacokinetic profiles of hesperetin may be altered by hyperuricemia. This study aimed to develop a highly sensitive and specific method for the determination of hesperetin in normal and hyperuricemia rats, and to compare pharmacokinetic profiles of hesperetin after oral administration between normal and hyperuricemia rats. Methods: Sprague-Dawley (SD) rats were randomly divided into one normal group (group A) and four hyperuricemia groups (group B, C, D, and E). Groups A, B, C, and D received a single dose (9–81 mg/kg) of hesperetin on Day 28, respectively, while group E received multiple doses (27 mg/kg) of hesperetin once daily for 28 days. Blood samples were collected at 10 different time points post-dose, and hesperetin was determined by ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS). Results: Compared with normal condition of group A, hyperuricemia of group C induced 48.19% and 19.57% decreases in Cmax and CL/F, and resulted in 58.25% and 19.48% increases in Tmax and AUC0-t for hesperetin, respectively. After 28 days of hesperitin treatment, Cmax of group E was significantly elevated than that of group C (p < 0.05). Hesperetin exhibited nonlinear pharmacokinetic properties in the range of 9–81 mg/kg in hyperuricemia rats. Conclusions: The pharmacokinetic parameters of hesperetin in hyperuricemia rats were reported for the first time. Intestinal injury may be ameliorated by hesperetin in hyperuricemia rats after 28 days’ treatment. These findings could provide more beneficial information to the mechanism and clinical applications of hesperetin.

scholarly journals Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

2020 ◽  
Vol 13 (9) ◽  
pp. 231
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Yong-Bok Lee
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Phase ◽  
Routes Of Administration ◽  
Administration Routes ◽  
Pharmacokinetic Profiles

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.

scholarly journals Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

2008 ◽  
Vol 11 (1) ◽  
pp. 88 ◽  
Author(s):  
Myung G. Lee ◽  
Young H Choi ◽  
Inchul Lee
Keyword(s):  
Diabetes Mellitus ◽  
Oral Administration ◽  
Protein Expression ◽  
Intravenous Administration ◽  
Insulin Treatment ◽  
Pharmacokinetic Parameters ◽  
Mrna Levels ◽  
Altered Pharmacokinetic ◽  
Intravenous And Oral Administration ◽  
Control State

To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

Lack of influence of the antidopaminergic drug domperidone on basal and TRH-stimulated TSH-serum levels after oral administration

1982 ◽  
Vol 101 (4) ◽  
pp. 550-554 ◽  
Author(s):  
K. W. Wenzel ◽  
J. Döring
Keyword(s):  
Oral Administration ◽  
Thyroid Function ◽  
Oral Absorption ◽  
Statistical Significance ◽  
Oral Intake ◽  
Serum Levels ◽  
The Novel ◽  
Antiemetic Drug ◽  
First Pass ◽  
The Difference

Abstract. Since antidopaminergic drugs are known to elevate basal and TRH-stimulated TSH-serum levels and since this effect was also shown after iv administration of the novel dopamine antagonistic agent domperidone, it was investigated, whether this antiemetic drug could interfere after oral intake with the evaluation of thyroid function. Oral domperidone caused a marked TSH-enhancement of TRH-induced TSH increments in 6 out of 14 euthyroid subjects, with no statistical significance, however. The difference between oral and parenteral influence as well as inter-individual changes are probably due to the varying first pass effect of the drug after oral absorption.

scholarly journals Experimental determination of the pharmacokinetic properties of trimethoprim and sulfamethoxazole combination in the blood serum of broiler chickens

2021 ◽  
Author(s):  
K Putecova ◽  
K Nedbalcova ◽  
I Bartejsova ◽  
M Zouharova ◽  
K Matiaskova ◽  
...  
Keyword(s):  
Oral Administration ◽  
Broiler Chickens ◽  
Animal Health ◽  
Pharmacokinetic Parameters ◽  
Serum Samples ◽  
Commercial Preparation ◽  
Single Oral Administration ◽  
Thermo Fisher Scientific ◽  
Medicinal Substances

A rapid, simple and highly efficient analytical method for the targeted determination of trimethoprim and sulfamethoxazole in serum samples has been developed and used to measure the pharmacokinetic curve of these medicinal substances after administration to chicken broilers. The pharmacokinetics properties of trimethoprim and sulfamethoxazole were investigated in clinically healthy broiler chickens after the single oral administration of the commercial preparation Methoxasol (Eurovet Animal Health, B.V., The Netherlands) at a dose of 0.275 ml/kg b.w. After a single dose drug administration, the chickens were sacrificed by decapitation under general anaesthesia by Isoflurin 1 000 mg/g (Vetpharma AH, Spain) and the blood was collected at precisely defined intervals: 15, 30, 45, 60, 90, 120, 180, 360 and 720 min after the administration. The serum concentrations of amoxicillin were determined using Q Exactive tandem mass spectrometer (Thermo Fisher Scientific, USA) in conjunction with liquid chromatography. The detected pharmacokinetic parameters of trimethoprim after the oral administration were C<sub>max</sub> = 2.1 ± 1.0 µg/ml; T<sub>max</sub> = 1.5 h; t<sub>½</sub> = 0.88 h; k<sub>el</sub> = 0.009 3 ± 0.001 1 1/h; AUC<sub>t</sub> = 2.901 ± 1.4 µg.h/ml; AUC<sub>∞</sub> = 2.907 ± 1.5 µg.h/ml; V<sub>d</sub> = 2.632 l/kg; Cl = 2.7 l/h. The pharmacokinetic parameters of sulfamethoxazole after the oral administration were C<sub>max</sub> = 47.1 ± 15.3 µg/ml; T<sub>max</sub> = 1 h; t<sub>½</sub> = 1.92 h; k<sub>el</sub> = 0.004 6 ± 0.000 3 1/h; AUC<sub>t</sub> = 89.676 ± 26.9 µg.h/ml; AUC<sub>∞</sub> = 94.612 ± 28.4 µg.h/ml; V<sub>d</sub> = 0.584 l/kg; Cl = 0.21 l/h. To the best of our knowledge, this is the first pharmacokinetic study of the combination of sulfamethoxazole and trimethoprim in broiler chickens.

scholarly journals Effects of Shaoyao-Gancao-Fuzi Decoction on the Pharmacokinetics of CYP3A4-Mediated Tofacitinib in Rats

2020 ◽  
Author(s):  
Li Lin ◽  
Yuan Wang ◽  
Sennan Shao ◽  
Wen Lin ◽  
Dan Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Oral Administration ◽  
Western Medicine ◽  
Control Group ◽  
Clinical Use ◽  
Pharmacokinetic Profiles ◽  
Pre Treatment ◽  
Cocktail Approach

Abstract Background: The combination of traditional Chinese medicine and western medicine is commonly accepted in clinics in China. Shaoyao-Gancao-Fuzi decoction (SGFD) has been extensively used to dispel wind, eliminate dampness and treat paralysis. Tofacitinib is approved for the treatment of rheumatoid arthritis. SGFD and tofacitinib could be used together for the treatment of rheumatoid arthritis.Methods: A cocktail approach was employed to assess the effects of SGFD on the activities of CYP450s. After pretreatment for 2 weeks with SGFD, a cocktail solution was given to rats 24 h after the last dose of saline or SGFD. Additionally, the pharmacokinetic profiles of oral administration of tofacitinib in rats, with or without SGFD pre-treatment were investigated.Results: The results showed that SGFD could induce the activity of CYP1A2 and inhibit the activity of CYP3A4. Furthermore, SGFD could significantly affect the pharmacokinetics of tofacitinib. Compared with control group, the AUC0-∞ of tofacitinib was increased from 13669.53 ± 4986.83 to 28706.69 ± 9563.13 ng/mL*h (p < 0.01), and the Cmax was increased from 8359.66 ± 1512.22 to 11332.51 ± 2791.90 ng/mL (p < 0.05).Conclusions: The system exposure of tofacitinib was increased by SGFD. The mechanism might be through inhibiting the activity of CYP3A4 and reducing the metabolism of tofacitinib in rats. The study will provide better guidance for the safe clinical use of SGFD and tofacitinib.

scholarly journals Prodrugs of 2',3'-dideoxyinosine(DDI): Synthesis and plasma concentration of DDI in rats via oral administration of an oil formulation.

1992 ◽  
Vol 7 (3) ◽  
pp. 203-207
Author(s):  
Takeo Kawaguchi ◽  
Tetsuya Hasegawa ◽  
Toshinobu Seki ◽  
Kazuhiko Juni ◽  
Yasunori Morimoto ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Oil Formulation

P3-283: Pharmacokinetics, pharmacodynamics, and safety of the novel bace inhibitor bi1181181 after oral administration of single ascending doses in healthy subjects

2015 ◽  
Vol 11 (7S_Part_16) ◽  
pp. P740-P741 ◽  
Author(s):  
Laurent Nicolas ◽  
Klaus-Peter Kammerer ◽  
Jennifer Schaible ◽  
Jasmin Link ◽  
Oliver Kleiner ◽  
...  
Keyword(s):  
Oral Administration ◽  
Healthy Subjects ◽  
The Novel ◽  
Bace Inhibitor
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