scholarly journals In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs

2016 ◽  
pp. 1917
Author(s):  
Myung Joo Kang ◽  
Kwang Ho Cha ◽  
Seung Yeob Kang ◽  
Donghan Won ◽  
Sun Woo Jang ◽  
...  
Keyword(s):  
Beagle Dogs ◽  
Gastroprotective Effect ◽  
Artemisia Asiatica

A Comparison of Anticoagulation Activity of a Potent Heparin Preparation in Different Test

1979 ◽  
Author(s):  
A.S. Bhargava ◽  
J. Heinick ◽  
Chr. Schöbel ◽  
P. Günzel
Keyword(s):  
Blood Clotting ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Thrombin Time ◽  
Beagle Dogs ◽  
Clotting Time ◽  
Relative Potencies ◽  
Heparin Preparation

The anticoagulant effect of a new potent heparin preparation was compared with a commercially available heparin in vivo after intravenous application in beagle dogs. The anticoagulant activity was determined using thrombin time, activated partial thromboplastin time and whole blood clotting time after 5, 10 and 30 minutes of application. The relative potency of the new heparin preparation (Scherinq) was found to be 1.62 to 2.52 times higher than heparin used for comparison (150 USP units/mg, Dio-synth). The anticoagulant properties of both preparations were also studied in vitro using dog and human plasma. The relative potencies in vitro correlated well with those obtained in vivo. Further characterization with amidolytic method using chromogenic substrate for factor Xa and thrombin (S-2222 and S-2238 from KABI, Stockholm) showed that heparin (Schering) contains 243 to 378 USP units/raq depending upon the test systems used to assay the anticoagulation activity and in addition, proves the validity of the amidolytic method.

scholarly journals Physiologically Relevant In Vitro-In Vivo Correlation (IVIVC) Approach for Sildenafil with Site-Dependent Dissolution

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 251 ◽  
Author(s):  
Tae Hwan Kim ◽  
Soyoung Shin ◽  
Seok Won Jeong ◽  
Jong Bong Lee ◽  
Beom Soo Shin
Keyword(s):  
Dissolution Kinetics ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Wet Granulation ◽  
Population Pharmacokinetic ◽  
Beagle Dogs ◽  
Concentration Time ◽  
In Vivo Dissolution

This study aimed to establish a physiologically relevant in vitro-in vivo correlation (IVIVC) model reflecting site-dependent dissolution kinetics for sildenafil based on population-pharmacokinetic (POP-PK) modeling. An immediate release (IR, 20 mg) and three sustained release (SR, 60 mg) sildenafil tablets were prepared by wet granulation method. In vitro dissolutions were determined by the paddle method at pH 1.2, 4.5, and 6.8 media. The in vivo pharmacokinetics were assessed after oral administration of the prepared IR and SR formulations to Beagle dogs (n = 12). The dissolution of sildenafil from SR formulations was incomplete at pH 6.8, which was not observed at pH 1.2 and pH 4.5. The relative bioavailability was reduced with the decrease of the dissolution rate. Moreover, secondary peaks were observed in the plasma concentration-time curves, which may result from site-dependent dissolution. Thus, a POP-PK model was developed to reflect the site-dependent dissolution by separately describing the dissolution and absorption processes, which allowed for estimation of the in vivo dissolution of sildenafil. Finally, an IVIVC was established and validated by correlating the in vitro and in vivo dissolution rates. The present approach may be applied to establish IVIVC for various drugs with complex dissolution kinetics for the development of new formulations.

In Vitro and In Vivo Evaluation of Olmesartan Medoxomil Microcrystals and Nanocrystals: Preparation, Characterization, and Pharmacokinetic Comparison in Beagle Dogs

2019 ◽  
Vol 16 (6) ◽  
pp. 500-510
Author(s):  
Rong Chai ◽  
Hailing Gao ◽  
Zhihui Ma ◽  
Meng Guo ◽  
Qiang Fu ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Olmesartan Medoxomil ◽  
Water Soluble ◽  
Size Reduction ◽  
Drug Dissolution ◽  
Beagle Dogs ◽  
Enhanced Solubility

Background: Olmesartan medoxomil (OLM) is a promising prodrug hydrolyzed to olmesartan (OL) during absorption from the gastrointestinal tract. OL is a selective angiotensin II receptor antagonist, with high drug resistance and low drug interaction. However, OLM has low solubility and low bioavailability. Therefore, it is extremely urgent to reduce the drug particle size to improve its biological bioavailability. Objective: The aim of the study was to improve the oral bioavailability of poorly water-soluble olmesartan medoxomil (OLM) by using different particle size-reduction strategies. Method: Raw drug material was micronized or nanosized by either jet or wet milling processes, respectively. The particle sizes of the prepared nanocrystals (100-300 nm) and microcrystals (0.5-16 μm) were characterized by DLS, SEM, and TEM techniques. Solid state characterization by XPRD and DSC was used to confirm the crystalline state of OLM after the milling processes. Results: We demonstrated that OLM nanocrystals enhanced solubility and dissolution in the non-sink condition in which high sensitivity was found in purified water. After 1 h, 65.4% of OLM was dissolved from nanocrystals, while microcrystals and OLMETEC® only showed 37.8% and 31.9% of drug dissolution, respectively. In the pharmacokinetic study using Beagle dogs, an increase in Cmax (～2 fold) and AUC (～1.6 fold) was observed after oral administration of OLM nanocrystals when compared to microcrystals and reference tablets, OLMETEC®. In contrast, OLM microcrystals failed to improve the oral bioavailability of the drugs. Conclusion: Particles size reduction to nano-scale by means of nanocrystals technology significantly increased in vitro dissolution rate and in vivo oral bioavailability of OLM.

External monitoring of 203Hg-labelled Dirofilaria immitis microfilariae in mice and dogs

Parasitology ◽  
1986 ◽  
Vol 92 (2) ◽  
pp. 463-469 ◽  
Author(s):  
F. W. Lengemann ◽  
R. B. Grieve ◽  
M. Chmielewicz ◽  
F. A. Kallfelz ◽  
J. R. Georgi
Keyword(s):  
Dirofilaria Immitis ◽  
Half Time ◽  
Beagle Dogs ◽  
External Monitoring

SUMMARYMicrofilariae of Dirofliaria immitis were labelled with 203Hg 2+in vitro and injected into irradiated mice and Beagle dogs. With irradiated mice it was possible to demonstrate microfilariae present in the blood and to detect 203Hg by external counting as long as 28 days after dosing. The 203Hg 2+ label had a half-time of 4–5 days; the amount of stable mercury in the labelling medium strongly influenced the survival of microfilariae in vivo. In dogs, external counting showed the lungs to be a major location of the microfilariae soon after reinjection into the host. Evidence was obtained that labelled microfilariae can circulate; however, the detection of dispersed microfilariae is difficult because of the relative insensitivity of the detecting system. For radiomercury the accumulation of the inorganic form in the liver and kidneys limits the long-term usefulness of 203Hg 2+ as a label if the organism being studied also accumulates in these organs.

scholarly journals Evaluation of Marine Diindolinonepyrane in Vitro and in Vivo: Permeability Characterization in Caco-2 Cells Monolayer and Pharmacokinetic Properties in Beagle Dogs

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 651 ◽  
Author(s):  
Ma ◽  
Guo ◽  
Elango ◽  
Bao ◽  
Wu
Keyword(s):  
Liquid Chromatography ◽  
Mass Spectrum ◽  
Tissue Distribution ◽  
High Performance ◽  
Intravenous Route ◽  
Pharmacokinetic Data ◽  
Beagle Dogs ◽  
Total Recovery

A marine fibrinolytic compound was studied for use in thrombolytic therapy. Firstly, the absorption and transportation characteristics of 2,5-BHPA (2,5-BHPA:2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-tertahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid, a novel pyran-isoindolone derivative with bioactivity isolated from a rare marine microorganism in our laboratory) in the human Caco-2 cells monolayer model were investigated. We collected 2,5-BHPA in the cells to calculate the total recovery, and its concentration was analyzed by LC/MS/MS (Liquid Chromatography/ Mass Spectrum/ Mass Spectrum). The results showed that 2,5-BHPA has low permeability and low total recoveries in the Caco-2 cells membrane. Pharmacokinetics and tissue distribution of 2,5-BHPA were investigated in beagle dogs using HPLC (High Performance Liquid Chromatography) after intravenous administration of three different doses (7.5, 5.0, 2.5 mg·kg−1). Pharmacokinetic data indicated that 2,5-BHPA fitted well to a two-compartment model. Elimination half-lives (T1/2) were 49 ± 2, 48 ± 2, and 49 ± 2 min, respectively; the peak concentrations (Cmax) were 56.48 ± 6.23, 48.63 ± 5.53, and 13.64 ± 2.76 μg·mL−1, respectively; clearance rates (CL) were 0.0062 ± 0.0004, 0.0071 ± 0.0008, and 0.0092 ±0.0006 L·min−1·kg−1, respectively; mean retention times (MRT) were 28.17 ± 1.16, 26.23 ± 0.35, and 28.66 ± 0.84 min, respectively. The low penetrability of 2,5-BHPA indicated that the intravenous route of administration is more appropriate than the oral route. Meanwhile, 2,5-BHPA showed a good pharmacokinetic profile in beagle dogs. The tissue distribution showed that 2,5-BHPA could quickly distribute into the heart, intestines, liver, stomach, spleen, lungs, testicles, urine, intestine, kidneys, brain, and feces. The concentration of 2,5-BHPA was higher in the liver and bile. Interestingly, 2,5-BHPA was detected in the brain. Taken together, the above results suggested that our work might be beneficial in the development of agents for thrombolytic treatment.

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