Publications by authors named "Humaira Majeed Khan"

10 Publications

  • Page 1 of 1

Genotoxic and cytotoxic assessment of sitagliptin and simvastatin alone and in combination.

Pak J Pharm Sci 2021 Sep;34(5(Supplementary)):1939-1944

Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University (LCWU), Lahore, Pakistan.

Type 2 Diabetes Mellitus (T2DM) patients are at high risk of Coronary Heart Disease (CHD) and need a global therapeutic intervention. A fixed-dose combination prescription medication containing anti-diabetic drug (Sitagliptin) and lipid lowering (Simvastatin) has recently been approved. Present study was designed to explore the potential synergistic toxic effects of sitagliptin and simvastatin at cellular level. MTT assay revealed the potential synergistic cytotoxic effect whereas Comet assay spotlighted the genotoxicity. MTT assay conducted on Vero cell lines revealed no significant change in proliferative activity upon treatment with simvastatin but cell survival percentage (CSP) decreased upon treatment with sitagliptin (51% at 1000μg/mL). However, combination of both drugs exhibited a better survival percentage except highest dose combination (1000:500μg/mL) which augmented antiproliferative effects rendering CSP 71.6%. The genotoxic assay spotted that Simvastatin produced less damage to DNA with the threshold of 500μg/ml whereas Sitagliptin significantly damage above the 250μg/mL, However, combination of drugs produced lesser damage than Sitagliptin alone. The findings concluded a non-genotoxic combination of sitagliptin and simvastatin which possess a least cytotoxic potential suggesting the safe use of the combination both in T2DM and CHD.
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September 2021

Anti myelosuppressant and hematopoietic activities of ethanolic fraction obtained from seeds of Carica papaya L.

Pak J Pharm Sci 2020 Nov;33(6):2651-2657

Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan.

Bone marrow suppression is one of the serious consequences of treatment with cytotoxic chemotherapeutic agents such as doxorubicin (DOX). It is very difficult to treat bone marrow suppression caused by anti-cancer drugs. This study was aimed to evaluate hematological effects particularly the antimyelosuppressant effects of ethanolic extract of papaya seeds at 200, 400 and 600 mg/kg daily dose for three weeks in doxorubicin induced hematopoietic suppression in rat model. Hematological parameters were assessed on weekly basis on days 0, 1, 7, 14 and 21. The alcoholic extract was found to cause remission of induced myelosuppression as indicated by a dose dependent increase in WBCs, neutrophils, lymphocytes, platelets, RBCs, Hb, hematocrit & mean corpuscular volume. However, the maximum dose (600mg/kg) of the extract showed maximum activity (p<0.05) in normalizing hematological parameters when compared with group B (induced group) and group A (controlled animals). These effects were compareable with those produced by Filgrastim 5µgm/kg used as standard or reference drug during these experiments. It is concluded from the results that papaya seeds possess myelostimulant activity and can be used to treat myelosuppression caused by chemotherapy. The drug can also be used for curing anemia, thrombocytopenia and immunological disorders characterized by myelosuppression.
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November 2020

Berberis lycium Royle. extracts attenuate inflammation and modulates hyperglycemia in alloxan induced diabetic rats.

Pak J Pharm Sci 2020 Jul;33(4(Supplementary)):1805-1813

College of Pharmacy, University of Sargodha, Sargodha, Pakistan.

Berberis lycium Royle (Berberidaceae) is traditionally used for the treatment of diabetes mellitus. Present study was conducted to determine the antioxidant, antidiabetic and anti-inflammatory effects of aqueous and methanolic whole plant extracts. Total phenolic contents were determined by Folin-ciocalteu method whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) method. In vitro anti-diabetic activity was determined using alpha amylase assay. Acute hypoglycemic activity was investigated on normoglycemic rats. Sub-acute anti-diabetic effects were investigated in alloxan induced diabetic rats for 14 days. Methanolic extract exhibited 183.5±1 mg/g Gallic acid equivalent (GAE) phenolic contents. The methanolic extract exhibited an IC50 of 242µg/mL and 37.26 mg/mL in antioxidant and alpha amylase inhibitory assays respectively. Administration of methanolic extract in normoglycemic rats exhibited significant anti-hyperglycemic effect at 90 and 120 min. Methanolic extract (500 mg/kg extract) significantly reduced blood glucose at day 14. Methanolic extract (500 mg/kg) significantly reduced the concentration of tumor necrosis factor (TNF-α) and interleukin (IL-6) along with reduction in total cholesterol and triglyceride levels in diabetic rats. Administration of methanol extract also improved the hepatic markers. The study suggested that the methanolic extract possessed antidiabetic effect that might be attributed to its alpha amylase, antioxidant and anti-inflammatory potential.
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July 2020

Population pharmacokinetics of meropenem among post-operative patients in Pakistan.

Int J Clin Pharmacol Ther 2021 May;59(5):398-408

Background: Meropenem, a potent carbapenem is considered the first choice for the empirical treatment of severe infections. Being a hydrophilic drug, more than 83% of the administered dose is eliminated through the renal route, and therefore, the kidney status of the patient may have a significant effect on meropenem clearance (CL).

Materials And Methods: The data of 205 samples obtained from 59 patients treated with meropenem at the General Hospital Lahore, Pakistan, was used for the development of a population pharmacokinetic (-popPK) model by using nonlinear mixed-effects modeling software. The effect of age, body weight, creatinine clearance (CRCL), and gender was observed on meropenem CL through a stepwise covariate modeling approach. Simulations of 1,000 mg q8h and 1,500 mg q12h over 3-hour infusion were performed based on the renal status of the patients.

Results: A two-compartment model was used for popPK analysis, and the values of the pharmacokinetic parameters for CL, V, V, and Q were 12.2 L/h, 21.7 L, 7.74 L, and 3.28 L/h, respectively. Meropenem CL was significantly influenced by CRCL, while no significant effect of body weight, age, and sex was observed. Both simulated dosage regimens were equally effective if CRCL of the patient was ≤ 100 mL/min, while 1,000 mg q8h produced better results if CRCL was > 100 mL/min.

Conclusion: The CL of meropenem depends on the renal status of the patients. The model can be used for dosing simulations based on the CRCL of the patients in order to tailor the dose of meropenem in Pakistani patients.
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http://dx.doi.org/10.5414/CP203790DOI Listing
May 2021

Population pharmacokinetics of ciprofloxacin in Pakistani patients suffering from enteric fever.

Int J Clin Pharmacol Ther 2021 Jan;59(1):47-54

Background: Ciprofloxacin, a potent carboxy-fluoroquinolone is proved to be effective against some resistant strains of Gram-negative bacteria. Being a hydrophilic drug, it is primarily excreted through the kidney; almost 66% of the clearance from the body occurs through glomerular filtration. Therefore, renal status of the patient can have a significant effect on ciprofloxacin clearance.

Materials And Methods: A total of 158 samples were collected from 32 patients treated with ciprofloxacin in the Surgical Unit-I of Lahore General Hospital, Pakistan. The data was used for the development of a population pharmacokinetic model by using non-linear mixed-effect modeling (NONMEM) software. The influence of different covariates (age, sex, body weight, serum creatinine (SeCR), and creatinine clearance (CRCL)) was observed on ciprofloxacin clearance (CL) and volume of distribution (Vd) by stepwise covariate modeling (SCM).

Results: A one-compartment model was used for ciprofloxacin population pharma-cokinetik (popPK) analysis, and the values for ciprofloxacin CL and Vd in the final model were estimated at 19.8 L/h and 74.9 L, respectively. Among all the tested covariates, only CRCL was proven to have significant influence on ciprofloxacin CL.

Conclusion: A strong relationship was found between the ciprofloxacin CL and renal status of the patients. The model can be used for dose tailoring in patients based on their CRCL values before the start of therapy with ciprofloxacin among Pakistani patients.
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http://dx.doi.org/10.5414/CP203823DOI Listing
January 2021

Amelioration of hyperglycaemia and modulation of pro-inflammatory cytokines by fractions in alloxan induced diabetic rats.

Arch Physiol Biochem 2020 Jul 11:1-10. Epub 2020 Jul 11.

Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan.

Present study is engrossed in identification of phyto-constituents from aerial part extracts of and appraisal of its anti-oxidant, anti-diabetic and anti-inflammatory potential based upon its folktale use. The methanol and -hexane fractions of aerial parts were analysed using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) respectively. Inhibitory concentration (IC) showed better results in case of methanolic extract for both in antioxidant (IC= 15.47 µg/mL) and alpha amylase (IC=18.75 µg/mL) assays. Significantly higher quantities of phenolic and flavonoid contents were present in methanolic extract. A significant correlation was found to be existed between these contents and IC of antioxidant assay. Alloxan induced hyperglycaemia declined along with improvement in lipid profile, C-reactive proteins (CRP), liver function tests (LFTs) and renal function tests (RFTs). Methanolic fraction (500 mg/kg) was also related to significant reduction in levels of inflammatory markers i.e. tumour necrosis factor-alpha, TNF- α (1.28 ± 0.13 g/L) and interleukin-6, IL-6 (98 ± 10.4 pg/L) as observed in diabetic rats. Based upon the above findings, the study suggests that methanolic fraction from aerial parts of the has better anti-diabetic profile which might be attributed to its alpha amylase, anti-oxidant and anti-inflammatory potential.
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http://dx.doi.org/10.1080/13813455.2020.1788099DOI Listing
July 2020

Effectiveness of pharmacist intervention model for chronic kidney disease patients; a prospective comparative study.

Int J Clin Pharm 2020 Apr 5;42(2):625-634. Epub 2020 Feb 5.

Lahore College for Women University, Institute of Pharmacy, 54000, Lahore, Pakistan.

Background Chronic Kidney Disease (CKD) is a global health concern with profound risk of cardiovascular disease, end stage renal failure and early mortality. Pharmacists' interventions during chronic disease management have been promising. However, evidence of pharmacist`s involvement in chronic kidney dosease is limited, particularly in developing countries. Objective To implement and evaluate the impact of pharmacist led intervention among pre-dialysis CKD patients. Setting Nephrology outpatient department of tertiary healthcare hospital. Methods Patients with chronic kidney disease from stage 2 to 4 attending hospital between October to December 2018 were enrolled in a multi-arm pre-post prospective study. Pharmacist interventional model consisted of disease education, dietary recommendations, counseling to improve medication adherence along with telephonic follow-up. Interventional group received pharmacist interventional model; whereas control group only received the usual care. The impact of pharmacist`s involvements were evaluated by observing the improvements in knowledge and adherence scores, physiological profile and body composition analysis assessed by body composition monitor (BF-508) at the end of follow-up of 3 months. Both intervention and control groups were compared by appropriate statistical techniques. Main outcome measure Knowledge and adherence scores, physiological profile and body composition analysis Results Total 120 patients (60 in each group) completed the study. Baseline variables were comparable between the two groups. Pharmacist interventional model causes significant improvement in knowledge score upon follow up between intervention and control groups (19.10 ± 3.65 versus 17.57 ± 3.55, p = 0.022). Likewise, Medication adherence score of intervention group significantly improved as compared to control group (p < 0.05) following the implementation of pharmacist intervention model. Physiological analysis showed small improvements in the intervention group but were not significant. Body composition analysis revealed higher body and visceral fat in both groups at the end of follow up. Conclusion Our analysis underscored that the tested pharmacist interventional model is an effective tool in improving disease knowledge and medication adherence among patients with chronic kideney disease.
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http://dx.doi.org/10.1007/s11096-020-00982-wDOI Listing
April 2020

Antiviral, embryo toxic and cytotoxic activities of Astragalus membranaceus root extracts.

Pak J Pharm Sci 2019 Jan;32(1):137-142

Department of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan.

Antiviral activity of Astragalus membranaceus aqueous and methanol root extracts was determined against Avian influenza H9 virus. Toxicity profile of extracts was evaluated using chicken embryos and BHK-21 cell line. Different concentrations (400, 200, 100, 50, 25. 12.5, 6.25 and 3.12μg/mL) of both aqueous and methanol extracts were mixed with standard virus inoculum (4HAunits) and incubated for 30minutes at 37°C prior to inject the chicken embryos. Chorioallantoic fluid harvested 72 hours post inoculation and evaluated for virus growth using hemagglutination assay. Same concentrations of both extracts without virus were injected in chicken embryos to evaluate embryo toxic activity as well. The cytotoxic activity of aqueous and methanol extracts was determined by MTT colorimetric assay using BHK-21 cells. Three concentrations (400, 200 and 100μg/mL) of aqueous and five concentrations (400, 200, 100, 50 and 25μg/mL) of methanol extract showed antiviral activity. None of the tested concentrations of aqueous and methanol A. membranaceus root extracts caused chicken embryo mortality. Cell survival percentage of aqueous extract was higher than 50 at all of the tested concentrations except 400μg/mL. Two concentrations (400 and 200μg/mL) of methanol extract showed cytotoxicity. It was concluded that aqueous and methanol roots extracts of A. membranaceus have antiviral activity and concentrations which were safe may be used for treatment of Avian influenza H virus infections.
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January 2019

Stability comparison of two dermal emulsions containing Hippophae Rhamnoides L. oil.

Pak J Pharm Sci 2017 Sep;30(5):1529-1534

Department of Pharmacy, Lahore College for Women University, Lahore, Pakistan.

Two formulations of multiple emulsion (ME-1 & ME-2) containing Hipophae rhamnoides L. oil were prepared. Along with emulsifiers (Abil EM 90, Synperonic F127), Magnesium and Zinc were used as stabilizer in ME-1 and ME-2 respectively. Both formulations were prepared using Two-Step Method and after preparation ME-1 and ME-2 were stored at different storage conditions i.e., 4°C, 25°C, 40°C, 40°C+ 75% RH for four weeks for stability evaluation. At 4°C ME-1 and ME-2 showed phase inversion and were excluded from further stability evaluation. While ME-1 and ME-2 both were stable at 25°C for a period of four weeks as no color change, phase separation and liquefaction occurred. ME-1 and ME-2 at 40°C, 40°C+ 75% RH exhibited change in color, liquefaction and phase separation. The decrease in viscosity and globule size whereas increase in electrical conductivity and pH were observed at 40°C, 40°C+ 75% RH for a period of four weeks. Multiple emulsion from Hippophae rhamnoide L. oil are unstable at refrigeration and high temperature conditions. These formulations must be placed at room temperature to increase their shelf life.
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September 2017

Glutathione sulfotransferase inhibition activity of a self-fermented beverage, Kanji.

Pharm Biol 2017 Dec;55(1):547-553

a Faculty of Pharmacy , University of the Punjab , Lahore , Pakistan.

Context: Kanji, a liquid preparation of roots of Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk. (Apiaceae), may inhibit glutathione sulfotransferase (GST) activity due to ferulic acid content.

Objectives: GST inhibition activity and characterization of Kanji and methanol extract of D. carota roots, and oral absorption pattern of ferulic acid from Kanji in rats.

Materials And Methods: GST inhibition activity of Kanji and methanol extract of D. carota roots in concentration range 0.001-100.00 mg/mL was determined using Sprague Dawley rat liver cytosolic fraction. Methanol extract upon column chromatography gave ferulic acid, which was used to characterize Kanji and determine its oral absorption pattern in Wistar rats.

Results: The GST inhibition activity of Kanji (100.00 μg/mL), methanol extract of D. carota roots (100.00 μg/mL) and tannic acid (10.00 μg/mL, positive control) was found to be 0.162 ± 0.016, 0.106 ± 0.013 and 0.073 ± 0.004 μM/min/mg, respectively. Different Kanji samples and methanol extract contained ferulic acid (0.222-0.316 mg/g) and 0.77 mg/g, respectively. Ferulic acid did not appear in plasma after oral administration of Kanji.

Discussion: Kanji having solid contents 80.0 μg/mL, equivalent to 0.0025 μg/mL ferulic acid, does not inhibit the activity of GST. The oral administration of Kanji, in human equivalent dose (528 mg/kg, 16.67 μg ferulic acid), to rats indicated poor absorption of ferulic acid.

Conclusion: Kanji having solid contents 14-36 mg/mL does not inhibit GST activity, hence may not interfere with drugs that are the substrates of GST, if taken concomitantly.
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http://dx.doi.org/10.1080/13880209.2016.1257030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130599PMC
December 2017
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