بلاول بھٹو کا پیغام
پی پی پی چیئر مین بلاول بھٹو زرداری کا خیر پور ناتھن شا ہ سے تعلق رکھنے والے ایم آ ر ڈی کے شہدا ء کی برسی پر پیغام
خیر پور ناتھن شاہ کے بارہ شہید کارکنان کو خراج عقیدت پیش کر تا ہوں ۔تاریخ ان شہیدوں کی قربانی کا ذکر سنہری حروف میں لکھے گی :بلاول بھٹو زرداری
پاکستان میں جمہوریت مفت میں نہیں ملی ،پیپلز پارٹی نے اس کی خاطر جانوں کی قربانیاں دیں :بلاول بھٹو زرداری
پی پی پی قیادت و کارکنان آج بھی جمہوریت کی حفاظت کے لیے سیاسی انتقام کا مقابلہ کر رہے ہیں ۔بلاول بھٹو زرداری
پارٹی کے شہیدوں کی قربانیاں رائیگاں نہیں جائیں گی ۔بلاول بھٹو زرداری
شہدا ء کوخراج عقید ت پیش کر نے کا درست طریقہ ان کے مشن کو آگے بڑھا نا ہے ۔بلاول بھٹو زرداری
پیپلز پارٹی اپنے نظریے اور جدو جہد سے ایک سیکنڈ کے لیے بھی غافل نہیں ہو ئی ۔بلاول بھٹو زرداری
پاکستانی عوام اب ایک نینو سیکنڈ کے لیے بھی جمہوری نظام کی معطلی برداشت کر نے کے لیے تیار نہیں ۔بلاول بھٹو زرداری
ضلع دادو کے قصبے خیر پور ناتھن شاہ میں آمرانہ حکومت نے پیپلز پارٹی کے 12کارکنوں کو شہید کیا تھا ۔12ستمبر 1983ء کو عبدالغنی ابڑو ،عبدالعزیز لاکھیر ،نظام الدین نائچ ،عبدالنبی کھوسو اور اﷲ واریو لانگاہ کو شہید کیا گیا تھا ۔
شاہنواز کھو سو ،حبیب اﷲ لغاری ،دیدار علی کھوکھر ،ضمیر حسین جاگیرانی ،اعجاز حسین کھو نھارو اور منظور احمد چانڈیو بھی شہدا میں شامل ہیں ۔
Since about the middle of the 19th century, numerous attempts have been made by Muslim scholars to interpret the Qur’ān to the modern world. By far the largest output of literature produced in this connection, whether in the form of commentaries, critiques or articles in periodical, has been in Urdu, English and Arabic. But whatever the medium of expression employed, the net result is still is far from satisfactory. Moulana Abul Kalam Azad (1888-1958) was one of the most notable Muslim figures in Sub-continent. The Tarjuman-al-Qur’ān is regarded on all hands as his main contribution to Islamic learning. His original plan was to prepare side by side two companion volumes to this great of his, one entitled Tafsir-al-Bayana affording a detailed commentary of the Qur’ān, the other entitled Muqaddima, to serve as prolegomena to the Tarjuman -al-Qur’ān. The circumstances of his life did not allow him the time that he needed to execute the two projects. Moulana Azad, s thinking and philosophy about commentary of the Qur’ān is very clear: ''Explain the Qur’ān in the manner of the Qur’ān ''. This paper attempts to enlighten many aspects of Moulana Azad, s commentary of Surat-al-Kahaf and explores his contribution and Comparative Analysis for other selected Urdu Tafasir of his era.
The aim of the present study is to evaluate the pharmacokinetics (PK) parameters of the cefixime in the local healthy human volunteers and to study the influence of its PK on the co-administration with omeprazole; rosuvastatin and clopidogrel on the pharmacokinetic of cefixime. The study was designed in three stages. In first stage of study, reverse phase high performance liquid chromatography (RP-HPLC-UV) method for the analysis of cefixime was developed and validated. In the second stage PK of cefixime was established in local healthy human volunteers while in the third stage potential drug-drug interaction of cefixime with concurrent administration of omeprazole, rosuvastatin and clopidogrel was investigated. A novel isocratic, simple, economic, precise, selective, and reproducible RP-HPLC-UV method of determination of cefixime and cefdinir (I.S) in human plasma was developed and validated. The cefixime was separated on a Supelco Discovery HS C 18 (150 x 4.6 mm, 5 μm) analytical column, fixed with Perkin Elmer C 18 (30 x 4.6 mm, 10 μm) guard cartridge. The methanol/acetonitrile (50/50 v/v):0.05% trifluoroacetic acid (19:81 v/v) was used as mobile phase. The flow rate was adjusted at 2.0 ml.min -1 . The temperature of the column was fixed at 50̊C and sample was injected using 20 μl loop and the eluents were monitored at a 285 nm. Sample preparation was based on a simple extraction procedure consisting of deproteination and extraction with 3 parts of 6% TCA solution (aqueous) followed by volume make up with the mobile phase. Separation of cefixime and cefdinir were achieved within 4 min. The present method demonstrated good values for specificity/selectivity, linearity (0.004-5.0 μg mL -1 ; r 2 >0.999 f), recovery I Abstract (>96% for cefixime), precision (%RSD <2.2 for cefixime), sensitivity (limit of detection: 1 ng mL -1 and lower limit of quantification: 4 ng mL -1 , stability of solutions, and robustness. The method was efficiently applied to a pharmacokinetic study in healthy adult volunteers. The PK study of cefixime in healthy human volunteers (n = 20) was conducted using single dose, open label study design. A strict inclusion and exclusion criterion was adopted. The physical, biochemical and hematological examination of every individual were conducted. Each individual volunteer was orally administered cefixime capsule (400 mg) with full glass of water (Ca ᴝ 250 ml) and blood samples were collected at preset time intervals and analyzed using HPLC. The plasma drug concentration was calculated and various PK parameters were calculated using PK summit ® a PK software. The mean ± SD of C max , T max AUC , AUC and AUMC of cefixime was 3.54 ± 0.55mg.ml -1 , 32.54 ± 5.81μg-hml -1 , 32.49 ± 5.99 μg-hml -1 and 246.67 ± 58.57 μg-h*h ml - 1 respectively. While the mean ± SD of Cl, Vd and MRT were 192.71 ± 31.46 ml/h/kg, 1200.13 ± 364.47 ml/kg and 7.23 ± 0.85h . The Pharmacokinetic analysis using non- compartment model for cefixime was also studied and the mean ± SD AUC , MRT, Cl and Vd were 33.492 ± 5.99 mg.ml -1 , 7.320 ± 0.853 h, 12270.252± 1958.550 ml/h/kg and 76485.611 ± 23318.799 ml, respectively. The present data reveal that most of the PK parameters of cefixime found in study are not significantly different from reported values in other nations and no need to adjust the dose under normal conditions. II Abstract The PK drug-drug interaction studies were carried out with same group of volunteers (n = 20) which participated in PK study with a wash out period of 3 weeks. Same protocol was adopted for inclusion and exclusion of volunteers. The single dose, two periods, two sequences, open labeled with wash out period of one week between the two interaction studies was designed. The plasma drug concentrations of cefixime following oral administration of cefixime (400 mg) alone and with simultaneous administration of omeprazole (40 mg) were investigated. The concentration of cefixime in plasma samples following simultaneous administration of cefixime (400 mg) and omeprazole (40 mg) capsule were calculated. The different PK parameters were determined to investigate interaction between cefixime and omeprazole. The C max of cefixime was significantly decreased from 3.545 ± 0.552 μg.ml -1 to 2.648 ± 0.356 mg.ml -1 whereas t max was non-significantly increase to 3.964 ± 0.118 to 4.00 ± 00 h. The decrease in AUC AUC ∞ and were also observed from 37.67 ± 3.77 μg-h ml -1 to 27.25 ± 5.94 μg-h ml - 1, 34.03 ± 5.496 μg-h ml -1 to 22.629 ± 5.99 μg-h ml - 1 and 435.415 ± 48.37, to 234.32 ± 52.43 μg-h*h/ml, respectively. The mean ± SD of Cl and Vd were reduced and MRT was increased from 192.71 ± 31.46 ml/h/kg to 188.70 ± 36.62, 1200.13 ± 364.47 to 1756.439 ± 900.81 ml/kg and 7.46 ± 4.55 h to 11.444 ± 5.42. The Pharmacokinetic analysis using non-compartment model for cefixime with simultaneous administration of omeprazole was also studied that also showed similar alteration in PK of cefixime following simultaneous administration of cefixime and III Abstract omeprazole. The alteration in drug plasma profile by changes in bound and un-bound fraction mainly affects the changes in the Cl and Vd. The change in the Cl and Vd will also alter the Vss and AUC. Similar protocol was adopted to study the PK drug drug interaction between the cefixime and rosuvastatin. Single oral dose of cefixime capsule (400 mg) alone and in combination with rosuvastatin (40 mg) were administered in healthy human volunteers (n = 20) using two periods, two sequence, open labeled, cross over design with washout period of 7 days between two treatments. Concurrent administration of cefixime with rosuvastatin significantly decreased C max , AUC and AUC ∞ of cefixime from 3.79 ± 0.69 mg.ml -1 to 2.88 ± 0.33 mg.ml -1 , 33.79 ± 6.22 μg.h ml -1 to 27.89 ± 3.80 μg.h ml -1 and from 29.06 ± 4.99 μg.h ml -1 to 25.01 ± 6.15 μg.h ml -1 , respectively. Similarly the Cl, MRT, and Vd also decreased significantly from 194.67 ± 54.23 to ± 42.48 ml/h/kg, 9.80 ± 5.22 to 8.65 ± 4.59 h and from 1435.24 ± 398.26 to 1246.21 ± 500.38 ml/h/kg, respectively. The non-compartment model analysis of the data for cefixime with co-administration with rosuvastatin showed significant decrease in AUC , and Cl from 33.49 ± 5.99 to 31.37 ± 3.89 mg.ml -1 , 12653.44 ± 7246.82 to 11893.69 ± 2761.52 ml/h/kg, respectively. while the MRT and Vd were also significantly decreased from 9.21 ± 1.21 to 8.49 ± 2.36 h and 97221.61 ± 33215.21 to 82341.41 ± 29368.67 ml. The decrease in the parameters may be due to the use of same class of transporter (SLC) both cefixime and rosuvastatin may either compete for same transporter or rosuvastatin may inhibit the transporter responsible for the transport of the cefixime across the G.I.T. membrane. IV Abstract The PK drug-drug interaction study of cefixime (400 mg) with clopidogrel (150 mg) was carried out with in healthy human volunteers (n= 20) using two period, two sequence, open labeled, cross over design with one week washout time between treatment periods. Various PK parameters like C max , T max , AUC, AUMC, MRT, t 1⁄2 β, Cl, Vd and t 1/2 β etc were calculated for cefixime single oral dose of cefixime following single oral dose of cefixime (400 mg capsule) alone and concurrent administration with clopidogrel (150 mg tablet). The data showed the decrease in the C max of cefixime from 3.35 ± 0.538 mg.ml -1 to 3.13 ± 1.13 mg.ml -1 . Whereas AUC , AUC and MRT of cefixime were also decreased from 37.67 ± 21.97 μg-h ml -1 to 32.97 ± 6.44 μg-h ml -1 , 34.04 ± 22.65 to 30.974 ± 3.664 and from 7.462 ± 5.22 h to 7.213 ± 3.198h, respectively. Moreover, non- compartment PK model was applied for cefixime with co-administration with clopidogrel was studied and the mean ± SD AUC , and Cl were decreased 41.27 ± 23.67 to 35.42 ± 6.90 mg.ml -1 , 12653.44 ± 7246.46 to 11627.21 ± 1930.77 ml/h/kg, respectively. While the MRT and Vd was decreased from 7.33 ± 0.86 to 6.96 ± 1.49 h and 76485.61± 23318.79 to 97295.95 ± 21281.29 ml, respectively. The t 1/2 β of cefixime changed from 3.64 ± 1.88 h to 6.96 ± 1.49 h with simultaneous administration of clopidogrel. The reason of alteration may be due to that; clopidogrel may competitively displace cefixime from protein and re-distribution of cefixime that may result in changes of PK parameters. The oral concurrent administration of the clopidogrel and cefixime is considered to be safe. The drug-drug interaction between the cefixime and clopidogrel may be classified as moderate type of drug-drug interaction." xml:lang="en_US