scholarly journals Pharmacokinetic Evaluation of Chalcone Derivatives with Antimalarial activity in New Zealand White Rabbits

2021 ◽  
Author(s):  
Shweta Sinha ◽  
Ajay Prakash ◽  
Bikash Medhi ◽  
Alka Sehgal ◽  
Daniela I Batovska ◽  
...  
Keyword(s):  
New Zealand ◽  
Antimalarial Activity ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Health Concern ◽  
Pharmacokinetic Studies ◽  
Chalcone Derivatives ◽  
New Zealand White Rabbits

Abstract Objective: Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. Results: In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL, 69.89 ± 5.49 µg/mL and 3.74 ± 1.64 µg/mL. The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.

scholarly journals Pharmacokinetic evaluation of Chalcone derivatives with antimalarial activity in New Zealand White Rabbits

2021 ◽  
Author(s):  
Shweta Sinha ◽  
Ajay Prakash ◽  
Bikash Medhi ◽  
Alka Sehgal ◽  
Daniela I Batovska ◽  
...  
Keyword(s):  
New Zealand ◽  
Antimalarial Activity ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Health Concern ◽  
Pharmacokinetic Studies ◽  
Chalcone Derivatives ◽  
New Zealand White Rabbits

Abstract Objective: Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. Results: In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL, 69.89 ± 5.49 µg/mL, and 3.74 ± 1.64 µg/mL. The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.

scholarly journals Pharmacokinetic evaluation of Chalcone derivatives with antimalarial activity in New Zealand White Rabbits

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shweta Sinha ◽  
Ajay Prakash ◽  
Bikash Medhi ◽  
Alka Sehgal ◽  
Daniela I. Batovska ◽  
...  
Keyword(s):  
New Zealand ◽  
Antimalarial Activity ◽  
Peak Plasma ◽  
Oral Route ◽  
Health Concern ◽  
Pharmacokinetic Studies ◽  
Chalcone Derivatives ◽  
New Zealand White Rabbits

Abstract Objective Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. Results In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL (intraperitoneal route), 69.89 ± 5.49 µg/mL (oral route), and 3.74 ± 1.64 µg/mL (oral route). The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.

scholarly journals Comparative in vivo study of pure drug and fast dissolving tablets of Simvastatin

2019 ◽  
Vol 9 (4-A) ◽  
pp. 490-496
Author(s):  
M. Suresh Babu ◽  
T. E. Gopalakrishna Murthy
Keyword(s):  
Rate Constant ◽  
Plasma Levels ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Pure Drug

The objective of this study was to investigate differences in the pharmacokinetic patterns between pure drug and an optimized  formulation of fast dissolving tablets  of Simvastatin. The formulations were administered to 2 groups of white New Zealand rabbits (n=6) following cross over design pattern and the plasma levels were measured using LC-MS/MS method. Pharmacokinetic parameters were determined for each formulation. The comparison of the plasma time curves of the dosage forms showed that each dosage form caused significant differences in the drug plasma levels.  The highest mean Cmax value was observed for optimized fast dissolving tablets (68.33 ± 0.42ng/ml) compared to  pure drug (27.72 ± 0.31ng/ml). The mean time taken to peak plasma concentration for (Tmax) following administration of pure drug  was  11.53 ± 0.011hours, while it was 6.09 ± 0.072 hour following administration of selected optimized fast dissolving tablets.The elimination rate constant (Kel) for pure drug and optimized fast dissolving tablets were found to be 0.58 ± 0.012h-1and 0.53 ± 0.014 h-1 respectively.  The absorption rate constant (Ka) for pure drug and optimized fast dissolving tablets were found to be 1.68 ± 0.01h-1and 5.53 ± 0.02h-1 respectively. The AUC0-αvalues observed with optimized fast dissolving tablets686.1.±2.07 nghr/ml in compared to pure drug values 191 ± 1.43 nghr/ml. Thus, the results of pharmacokinetic studies indicated rapid and higher oral absorption of Simvastatin when administered as its fast dissolving tablets. Both Ka and AUC were markedly increased by fast dissolving tablets. Keywords: LC-MS/MS, Simvastatin, fast dissolving, In-vivo studies, pharmacokinetic parameters.

scholarly journals OPTIMIZATION OF STATISTICALLY DESIGNED ACECLOFENAC FAST DISSOLVING TABLETS EMPLOYING STARCH GLUTAMATE AS A NOVEL SUPERDISINTEGRANT

2019 ◽  
pp. 77-88
Author(s):  
R. SANTOSH KUMAR ◽  
SAHITHI MUDILI
Keyword(s):  
Drug Release ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Studies ◽  
Disintegration Time ◽  
Short Period ◽  
Dissolution Efficiency

Objective: To optimize aceclofenac fast dissolving tablets employing starch glutamate as novel superdisintegrant by 23factorial design to improve bioavailability and enhance patient compliance. Methods: Starch glutamate was prepared by the esterification process. Starch glutamate physical and micromeritics properties had been evaluated and the prepared starch glutamate was used as a superdisintegrant for the formulation of the fast dissolving tablets of aceclofenac by direct compression method and optimized by employing 23factorial design. The prepared aceclofenac fast dissolving tablets were evaluated for post compression parameters as well as in vitro and in vivo release characteristics. Optimized formulation stability studies were performed at accelerated conditions for 6 mo as per ICH and WHO guidelines. Results: The prepared starch glutamate was amorphous, insoluble in aqueous and organic solvents were tested. Fast dissolving tablets of aceclofenac were formulated by employing starch glutamate as a superdisintegrant showed good tablet properties and showed an increased dissolution efficiency of the drug. Among all the formulations (F1 to F8), the formulation F8 containing 5% concentration of starch glutamate, croscarmellose sodium and, crospovidone as a superdisintegrants showed 99.7±0.15% of drug release within 5 min. Whereas the formulation F2 containing 5% concentration of starch glutamate, drug release characters were comparable to the formulation F8. Optimized formulation F2 attained peak plasma concentration within a short period and showed increased relative bioavailability of the drug. Conclusion: From the physical properties, disintegration time, in vitro dissolution studies and pharmacokinetic studies, it was concluded that fast dissolving tablets of aceclofenac tablets formulated by employing starch glutamate as a superdisintegrant enhanced the dissolution efficiency and improved the bioavailability of the drug as compared to the pure drug and stable.

scholarly journals Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

2015 ◽  
Vol 51 (3) ◽  
pp. 591-605 ◽  
Author(s):  
Ankita Gupta ◽  
Gaurav Tiwari ◽  
Ruchi Tiwari ◽  
Rishabh Srivastava ◽  
A. K. Rai
Keyword(s):  
New Zealand ◽  
In Vitro Release ◽  
Diffusion Method ◽  
Pharmacokinetic Studies ◽  
Hpmc Capsules ◽  
New Zealand White Rabbits ◽  
S 100 ◽  
Calcium Pectinate ◽  
Enteric Coated

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer.

scholarly journals A new sensitive HPLC/UV method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma: Application to in-vitro and in-vivo evaluation of paclitaxel polymeric nanoformulations

2021 ◽  
Vol 20 (9) ◽  
pp. 1949-1959
Author(s):  
Mirina Sakhi ◽  
Abad Khan ◽  
Ismail Khan ◽  
Zafar Iqbal ◽  
Sumaira Irum Khan ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Chromatographic Method ◽  
Pharmacokinetic Studies ◽  
Good Resolution ◽  
In Vivo Evaluation ◽  
Spiked Plasma ◽  
Standard Solutions

Purpose: To develop a simple, novel, sensitive and rapid reverse phase high performance liquid chromatographic method for simultaneous determination of paclitaxel, sorafenib and omeprazole in standard solutions and spiked human plasma and its application to the in-vitro and in-vivo evaluation of paclitaxel polymeric nanoparticle formulations.Methods: The method was tested for the assessment of paclitaxel, omeprazole and sorafenib using tamoxifen citrate as internal standard. The analysis was performed at a wavelength of 235 nm using Thermo HS C18 column, 40 °C column oven temperature, acetonitrile and water (70:30 v/v, pH 3.37 adjusted with phosphoric acid) as a mobile phase and at a flow rate of 0.8 ml/min. All analytes were extracted by simple protein precipitation method using acetonitrile. The linearity was assessed in the concentration range of 1 - 2000 ng/mL for paclitaxel, omeprazole and sorafenib.Results: The developed chromatographic method effectively separated omeprazole, paclitaxel, sorafenib and IS with retention time of 3.93, 5.18, 6.43 and 9.93 min, respectively. The chromatograms of the three target compounds and IS showed good resolution and peak separation. The LOD of the method was 1, 5 and. 5 ng/mL while the LOQ was 2, 7.5 and 10 ng/mL, for paclitaxel, sorafenib and omeprazole, respectively.Conclusion: The proposed RP-HPLC–UV method for the assessment of paclitaxel, sorafenib and omeprazole in standard solutions and spiked plasma is simple, economical, sensitive and robust. The method is also suitable for the analysis of paclitaxel in nanoformulations and for its pharmacokinetic studies in an animal model.

scholarly journals In Vivo Antimalarial Activity of Leaf Latex of Aloe melanacantha against Plasmodium berghei Infected Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Gebrehiwot Kiros Gebremariam ◽  
Haile Kassahun Desta ◽  
Tekleab Teka Teklehaimanot ◽  
Tsgab Gebrecherkos Girmay
Keyword(s):  
Weight Loss ◽  
Survival Time ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Health Concern ◽  
Dependent Manner ◽  
Loss Reduction ◽  
Oral Toxicity

Background. Malaria is a major health concern in the world in general and developing countries in particular. Nowadays, the control of malaria has ended up steadily more complex due to the spread of drug-resistant parasites. Medicinal plants are the verifiable source of compelling antimalarial drugs. The present study was aimed to assess the in vivo antimalarial activity of leaf latex of A. melanacantha against Plasmodium berghei in mice. Methods. Acute oral toxicity study of the leaf latex was assessed in mice up to a dose of 2,000 mg/kg. A four-day suppressive model was utilized to investigate the antimalarial activity of the plant. Three extract doses, 100, 200, and 400 mg/kg/day, doses of the plant leaf latex, chloroquine, 10 mg/kg (positive control) and distilled water, and 10 mL/kg (negative control) were administered to mice. Percent parasitemia suppression, packed cell volume, mean survival time, body weight, and rectal body temperature were used to determine antimalarial activity. Results. Test groups treated with 100, 200, and 400 mg/kg of the latex showed a significant parasitemia suppression in dose dependent manner compared to the negative control with an IC50 of 22.63 mg/ml. Mice treated with 100, 200, and 400 mg/kg have shown parasitemia suppression of 14.86%, 29%, and 43.2%, respectively. The chemosuppression was significant ( P < 0.05 ) at all doses compared to the negative control. Similarly, mice treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg have shown a significant survival time compared to the negative control. At the same time, weight loss reduction was observed within the test groups treated with 100 mg/kg and 200 mg/kg of the latex while the test groups treated with 400 mg/kg had showed almost no weight loss reduction. The latex also reversed the PCV reduction significantly ( P < 0.05 ) at 200 mg/kg and 400 mg/kg doses and prevented rectal temperature dropping significantly ( P < 0.05 ) at all doses. Conclusion. The leaf latex of A. melanacantha has shown significant antimalarial activity against P. berghei in mice supporting the genuine traditional antimalarial usage of the plant.

Extracorporeal Enzymatic Removal of Low Density Lipoproteins in Rabbits: Efficacy and Safety

1993 ◽  
Vol 16 (4) ◽  
pp. 218-228 ◽  
Author(s):  
S.D. Shefer ◽  
J. Ferreira ◽  
C. J-P. Mullon ◽  
R. Langer
Keyword(s):  
New Zealand ◽  
Plasma Cholesterol ◽  
Low Density Lipoproteins ◽  
The Body ◽  
Cholesterol Concentration ◽  
Enzyme Assays ◽  
Low Density ◽  
Plasma Cholesterol Concentration ◽  
New Zealand White Rabbits

An extracorporeal circuit incorporating a plasma separator reactor (PSR) was designed to modify low density lipoproteins (LDL). The PSR was tested in vivo with hypercholesterolemic New Zealand White rabbits. The bioreactor enzymatically converts LDL to a form that can be removed by the body at an enhanced rate. The physiological response of hypercholesterolemic New Zealand White rabbits to 90 minute extracorporeal treatments was monitored. The total plasma cholesterol concentration in the treated rabbits fell sharply (up to 40% decrease) during and following the treatment. Results of safety tests indicate no significant enzyme leaching from the device, no disruption or damage to erythrocytes, no increase in white blood cell count and no liver damage as indicated by five enzyme assays. All safety measurements suggest that the treatment is safe.

Polymorphonuclear leukocyte cytoplasts mediate acute lung injury

1988 ◽  
Vol 65 (2) ◽  
pp. 706-713 ◽  
Author(s):  
V. B. Antony ◽  
C. L. Owen ◽  
D. English
Keyword(s):  
Acute Lung Injury ◽  
New Zealand ◽  
Lung Injury ◽  
Polymorphonuclear Leukocyte ◽  
Lung Lavage ◽  
Lung Weight ◽  
Endothelial Monolayers ◽  
New Zealand White Rabbits

Injection of phorbol 12-myristate 13-acetate (PMA) into polymorphonuclear leukocyte (PMN)-depleted, PMN cytoplast-repleted New Zealand White rabbits caused the development of acute lung injury in vivo. PMN cytoplasts are nucleus- and granule-free vesicles of cytoplasm capable of releasing toxic O2 radicals but incapable of releasing granule enzymes. PMN cytoplasts when activated by PMA reduced 66 +/- 12.7 nmol of cytochrome c compared with 2.6 +/- 0.7 nmol in their resting state and did not release a significant quantity of granule enzymes (P greater than 0.05). Injection of PMA into New Zealand White rabbits caused a significant decrease (P less than 0.05) in the number of circulating cytoplasts. Increases in lung weight-to-body weight ratios in PMA-treated rabbits (9.8 +/- 0.5 X 10(-3] compared with saline-treated rabbits (5.3 +/- 0.2 X 10(-3] were also noted. Levels of angiotensin-converting enzyme in lung lavage as well as the change in alveolar-arterial O2 ratio correlated with the numbers of cytoplasts in lung lavage (P = 0.001, r = 0.84 and P = 0.0166, r = 0.73, respectively). Albumin in lung lavage increased to 1,700 +/- 186 mg/ml in PMA-treated rabbits from 60 +/- 30 mg/ml in saline-treated rabbits. These changes were attenuated by pretreatment of rabbits with dimethylthiourea (DMTU). In vitro, cytoplasts were able to mediate increases in endothelial monolayer permeability. This was evidenced by increases in fractional transit of albumin across endothelial monolayers when treated with PMA-activated cytoplasts (0.08 +/- 0.01 to 0.28 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document