Open Access Minireview Article

Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

Md. Jahidul Hasan

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/jpri/2018/v25i430104

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.  

Open Access Original Research Article

An In vivo Antiplasmodial Activity of Aqueous and Ethanol Crude Plant Extracts of Phyllanthus fraternus Using Plasmodium berghei Infected balb/c Mice

Daniel Amiteye, Abraham Quarcoo, Bright K. Azumah, George M. Aryitey, Lateef A. Oseni, Stephen Antwi, Bernardine Teiko Korletey

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/jpri/2018/v25i430105

Background: Phyllanthus fraternus is a tropical plant that has numerous pharmacological activities such as blennorrhagia, colic, diabetes, dysentery, fever, flu, tumours, jaundice, vaginitis, dyspepsia, anti-inflammatory, antioxidant, anticoagulant, anti-diabetic, antiviral and analgesic. The study evaluated in vivo anti-plasmodial activity of aqueous and ethanol crude plant extracts of Phyllanthus fraternus using Plasmodium berghei infected Balb/c mice.

Methodology: The preparation of the aqueous crude extract was done by boiling 195 g of the dried plant material in 4 L of water for 30 minutes and cooled. The resultant extract was filtered through a cotton wool and put in an oven at 50°C to concentrate it before it was pre- freeze and lyophilized into powder using a freeze dryer (Heto powder dry LL 300, Sapa). Similarly the preparation of the ethanol crude extract was obtained by simple maceration of 195 g of dried sample of the plant in 2 L aqueous ethanol (1.4 L of ethanol plus 0.6 L of distilled water) for 72 h. It was then filtered through cotton wool and subjected to rotary evaporator (ILA CCA-1111 Japanese branch) to evaporate the ethanol and then pre-freeze and freeze- dried. The crude extracts were screened for their phytochemical constituents which showed the presence of secondary metabolites. The LD50 of both extracts were investigated using Sprague-Dawley rats and found to be greater than 5000 mg/kg. The in vivo antiplasmodial activity (percentage parasitaemia (%P) and the percentage chemo-suppression (%C)) of the extracts were evaluated using Balb/c mice.

Results: The aqueous and ethanol extracts established modest antiplasmodial activity in a dose dependent manner. The standard drug (coartem 2 mg/kg) with percentage parasitaemia (%P) of 28.57±4.70 and 2.48±0.48 caused percentage chemosupression (%C) of 44.38±7.63 and 81.27±2.07 in day four and six respectively. The test groups (aqueous and ethanol extracts) for two different doses (100 mg/kg and 200 mg/kg) each administered with percentage parasitaemia (%P) 39.67±1.35, 39.58±1.64, 37.32±2.37, 36.23±1.99 and 10.24±1.32, 9.33±0.66, 8.61±0.96, 7.27±1.26 caused percentage chemosuppressions (%C) of 22.78±2.20, 22.96±2.66, 27.35±3.84, 29.48±3.23 and 22.54±9.93, 29.43±4.99, 34.87±6.66, 44.99 ±5.98 in day four and six respectively. The aqueous extract demonstrated better inhibition of plasmodium in doses 100 mg/kg and 200 mg/kg with chemosuppressions (27.35 ± 3.84 and 29.48 ± 3.23) respectively compared with the ethanol extract of the same doses 100 mg/kg and 200 mg/kg with chemosuppressions (22.78 ± 2.20 and 22.96 ± 2.66) respectively. The activity of the standard drug, coartem at 2.0 mg/kg was significantly higher (p< 0.05) with chemosupression (44.38±7.63) than those of the extracts. The extracts were also screened for phytochemicals for which some were found in the extracts which have previously been implicated as antiplasmodial agents. The LD50 of both extracts were investigated and found to be greater than 5000 mg/kg.

Conclusion: The aqueous and ethanol crude plant extracts of P. fraternus possess antiplasmodial activity and would be useful in the search for novel antimalarial agents.

Open Access Original Research Article

Anticonvulsant Potential of Dichloromethane Extract of Aspilia africana Leaf in Mice

Kemelayefa James Ozakieoniso, Hope Delesi Kagbo

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/jpri/2018/v25i430106

Aim: The study was carried out to determine the anticonvulsant potential of dichloromethane leaf extract of Aspilia africana.

Study Design: Three seizure models namely: Pentylenetetrazole (PTZ), strychnine (STC) and maximal electroshock (MES) were used, motor coordination behavior of the animals were also assessed.

Place and Duration of Study: The study was carried out between the months of October and November, 2017 at Pharmacology laboratory, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria.

Methodology: The powdered leaves of A. africana (2000 g) were extracted with 10 liters of 100% dichloromethane. Doses of 25, 50, 100 and 200 mg/kg were administered to the test animals.

Results: The chemical models, STC & PTZ showed 50% & 100% survival respectively. The delayed onset of seizure suggested anti-seizure potential of dichloromethane extract of A. Africana leaf with the maximal latency period of seizure recorded in the 25 mg/kg dose within the following chemical models, this was significant, P = .05 compared to the normal control. The MES method showed that at doses of 25 & 50, 100 mg/kg, the animals were 66.7% & 50% free of hind limb tonic extension (HLTE). Furthermore, there was reduced motor coordination potential at 25 mg/kg by 68.5%, which was significant at the level of, P = .05, compared to healthy control.

Conclusion: From the preceding, it can be seen that the dichloromethane leaf extract of A. Africana has antiseizure potential.

Open Access Original Research Article

Assessment the Photo-neutron Contamination of IMRT and 3D-Conformal Techniques Using Thermo-luminescent Dosimeter (TLD)

Ebtesam M. Mohamedy, Hassan Fathy, Wafaa M. Khalil, Nadia L. Helal, Ehab M. Attalla

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/jpri/2018/v25i430107

The aim of the study is to evaluate the dependence of photo-neutron production on field size, depth in phantom and distance from isocenter and also to calculate the equivalent neutron doses for PTV and OARs of IMRT and 3DCRT techniques using TLD (600/700).The Linac Siemens Oncor installed at Nasser Institute, Cairo, Egypt. TLDs, Neutron Monitor, Ionization chamber were provided by NIS, the duration of the study was from November 2017 to July 2018. 5 prostate cancer cases were selected treated with high energy beam (15MV) Linear accelerator using 3DCRT and IMRT treatment plans. The OARs were bladder, rectum and femur. Once the plans were completed, there were copied from the planning system onto the RW3 slab phantom in which pairs of TLD chips (600/700) were placed at the exact site of PTV and OARs. The results showed that: The measured photo-neutron decreases from 0.2 mSv/Gy to 0.09 mSv/Gy as increases field sizes from 2x2 cm2 to 20x20 cm2. The measured photo-neutron was maximum at dmax =0.15 mSv/Gy and decreases gradually as increases the depth in phantom reaches to 0.07 mSv/Gy at 10cm depth in phantom. The measured photo-neutron decreases from 1.5 mSv/Gy to 0.02 mSv/Gy when measured at isocenter and at 100cm along the patient couch. Using 3DCRT for PTV and OARs were ranging from 0.027 to 0.39 mSv per photon Gy and for IMRT were 0.135 to 2.34 mSv per photon Gy. In conclusion the photo-neutron production is decreases as increases field size and distance from isocenter along patient couch while increases with depth in phantom up to dmax and decreases gradually as increases depth in phantom. IMRT requires longer beam-on time than 3DCRT leading to worse OARs sparing and increase the production of photo-neutrons than 3DCRT.

Open Access Original Research Article

Evaluation of Liver Protective Activity of Moringa oleifera Bark Extract in Paracetamol Induced Hepatotoxicity in Rats

Rajibul Islam, Md. Jahir Alam, Sara Benojir Shanta, Md. Habibur Rahman, Sultan Mahmud, Abdus Sobahan Khan

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/jpri/2018/v25i430108

Background: Moringa oleifera has been used in folk medicine to alleviate several diseases. In the present study, ethanolic extract of Moringa oleifera bark has been investigated to study its potential on paracetamol induced hepatotoxicity on model rats.

Methods: Rats (150–200 gm) were divided into 5 groups containing 6 animals each. Acute hepatotoxicity was induced by paracetamol (600 mg/kg body weight) administered once daily for one week whereas the extract of investigated plant was given orally throughout the whole experiment at 250 and 500 mg/kg body weight. Silymarin (100 mg/kg body weight) was given orally as standard hepatoprotective drug. The level of hepatic injury recovery was determined by the estimation of liver enzymes like SGPT, SGOT, ALP, Bilirubin, Total protein, globulin and Albumin.

Results: Treatment with MO extract as well as standard hepatoprotective agent silymarin ameliorated plasma levels of hepatic enzymes. Body weight was improved significantly by MO extracts (p < 0.01), whereas liver weight was recovered insignificantly. SGPT, SGOT and ALP levels were improved very highly significantly (p<0.001) and highly significantly (p<0.01) at MO 250mg dose. While at the dose of 500 mg/kg ameliorated SGPT Level very highly significantly (p<0.001), SGOT Level highly significantly (p<0.01) but insignificant to ALP level.  

Conclusion: The biochemical parameters provide evidence that the ethanolic extract of of Moringa oleifera bark has shown hepatoprotective activity.