Evaluation of pharmacokinetic interactions of amoxicillin with ranitidine in healthy human volunteers of Karachi, Pakistan.

Polypharmacy may be considered as the customary practice to provide optimum care services to patients but inter resulted in augmented probability of multiple drug interaction. Keeping in view the importance of drug interaction possibility, this study was designed to evaluate the effect of ranitidine on pharmacokinetics of amoxicillin in the local population of Karachi, Pakistan. Amoxicillin and ranitidine are the most commonly prescribed drugs to treat duodenal ulcer caused by Helicobacter pylori. The current investigation was carried out as a single center, open label, two phase, single dose, randomized way in cross over manner to evaluate the potential of pharmacokinetic interaction among amoxicillin formulation and ranitidine in adult healthy male volunteers. Post dosing blood samples were collected at multiple time points that are 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours after administering amoxicillin 250mg capsule with and without ranitidine. For estimation of amoxicillin concentration in plasma, an HPLC method was developed and validated. The solvent system consisted of 0.025M phosphate buffer: acetonitrile (94:6 v/v). C18 column was employed with a flow rate of 1.0 ml/minute and at 230nm. A linear pattern with a correlation coefficient of 0.999 in the concentration ranges of 25µg/mL to 0.097µg/mL for amoxicillin and 25µg/mL to 0.048µg/mL for ranitidine was observed. Amoxicillin retention time was about 8 minutes and ranitidine retention time was around 12 minutes. Amoxicillin levels were computed and the concentrations were applied to calculate the pharmacokinetic parameters. Pharmacokinetic parameters were estimated by Kinetica TM 4.4.1 (Thermo Electron Corp. USA). The analysis of variance (two way) and t test (two one sided) were applied on log transformed pharmacokinetic parameters of amoxicillin. The Tmax was determined between amoxicillin alone and amoxicillin with ranitidine by Friedman test. The 90% confidence interval values for Cmax(calc) (0.687-0.743) and Tmax(calc) (1.148-1.742) for amoxicillin with or without ranitidine were not found within the FDA acceptable limits of 0.8-1.25. Study demonstrated the significant reduction in peak plasma levels of amoxicillin in presence of ranitidine. It is advisable to administer both drugs with time interval to avoid such interactions and increases in the bactericidal efficacy of amoxicillin.

Optimization of empagliflozin immediate release tablets (10 mg) using central composite rotatable design with response surface methodology.

Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.

Spectroscopic interactions of non-insulin-dependent diabetes mellitus with levocetirizine.

Non insulin dependent diabetes mellitus (NIDDM) drugs such as glibenclamide and metformin is employed to heterogeneous disorder characterized by alteration in production of glucose due to impairment of both insulin secretion and insulin action. These patients might suffer with allergic rhinitis and in this case, there is a possibility to maintain patient on levocetirizine, an anti-allergic drug commonly used in rhinitis. The object of the present study is to detect possible interaction between glibenclamide or metformin with levocetirizine Current study was performed using UV spectroscopic technique sing simultaneous equation in pH simulated to gastric juice (pH 1), pH 4, pH 7.4 and in pH 9. All drugs followed Beer Lambert's Law. Results showed that glibenclamide and metformin can increase or decrease availability of levocetirizine and in the same way levocetirizine can alter availabilities of glibenclamide and metformin in different pH. Hence, drug interaction between glibenclamide or metformin with levocetirizne occurred. This may be due to his may be due to the charge transfer or binding capabilities of these drugs which resulted in significantly changed availability of NIDDIM as well as levocetirizine. Therefore, co-administration of these drugs should be avoided and furtherinvestigations at clinical and pre-clinical levels should be done.

Hepatotoxicity induced by chronic suppurative otitis media in rats and effects of ceftazidime and amikacin on it.

Chronic suppurative otitis media (CSOM) is the chronic inflammation with perforation of middle ear. If CSOM is not treated, it may cause secondary inflammation of liver with elevated liver enzymes and histological changes. Present study is aimed to observe the hepatotoxic effects due chronic suppurative otitis media (CSOM) in CSOM induced rats and alsoto observe the effects of ceftazidime and amikacin to attenuate hepatotoxicity due to CSOM. Liver enzyme tests and histological examinations were performed on rats divided into different groups as G1 (negative control), G2 (positive control), G3 ceftizidime (15mg/kgintraperitonelly) and G4 amikacin (15mg/kg). One-way ANOVA showed that liver enzymes were significantly increased (p=0.000 and F value 6.899) except gamma glutamic transferase in G2 (rats with CSOM without treatment) from G1 (negative control without CSOM) with histological damage of liver. These hepatotoxic effects were attenuated or recover with proper treatment with potent antibiotics (ceftazidime and amikacin). Therefore, study showed that chronic suppurative otitis media can induce hepatic toxicity including elevated liver enzymes level and inflammation, aggregation or infiltration in liver cells in rat model with reversible hepatic damage. If CSOM is treated with adult dose of ceftazidime or amikacin, it may attenuate the damage and prevent risk of liver damage.

Determining the release kinetics of risperidone controlled release matrices to treat schizophrenia.

Risperidone is an atypical antipsychotic agent clinically used to treat schizophrenia, bipolar diseases, and autism. Usually, the frequency of doses is twice daily. In the present study, risperidone controlled release matrices formulated using hydrophilic and hydrophobic polymers. The tablets were prepared by direct compression. The pre-compression and post-compression properties were assessed, along with swelling studies. The morphology of particles observed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The stability study on the drug was performed using thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). The optimized formulation was prepared with the help of hydrophilic polymer K100M (40% ratio). Furthermore, release kinetics had investigated. The release pattern of optimized formulation FT5 fitted best to zero-order kinetics and showed excellent release characteristics. The model-independent approach had been used, formulations FT6 and FT8 showed resemblance with FT5 in all three media, respectively. The once daily formulation of risperidone could be beneficial for schizophrenia patients and their caregivers and will improve patient compliance.

Staphylococcal resistance against five groups of life saving antibiotics in the year 2003-2005.

In the year 2003 to 2005 a prospective study was conducted to find out the predominance of Staphylococcus (Staphylococcus aureus) resistance pattern in opposition to five life saving antibiotics as these are the sole agents to treat critically ill patients in hospitals. During the period of two years almost 2500 samples of bacterial culture were taken from different pathological laboratories and hospitals in Karachi. Among these 1500 were Gram positive cocci and 1000 samples were identified as Staphylococcus aureus. Life saving antibiotics were taken from five different groups and by mean of disk diffusion technique antibiogram of Staphylococcus aureus against these antibiotic were determined. During the course of study imipenem showed 11%, amikacin exhibited 58%, cefipime showed 31%, vancomycin and piperacillin/tazobactam displayed 24% resistance against Staphylococcus aureus. Imipenem was found to be most effective against Staphylococcus aureus.Resistance to other antibiotics developed quickly in Staphylococcus aureus collected from clinical areas where these antimicrobial agents are extensively used.

Antimicrobial susceptibility pattern of clinical isolates from cases of ear infection using amoxicillin and cefepime.

The aim of the present study was to determine the sensitivity pattern of clinical isolates of otitis media. During the last few decades, the occurrence of otitis media seems to have been rising probably because of prevalence of multidrug-resistant Pseudomonas aeruginosa and ß-lactamase producing Staphylococcus aureus in the pathogenesis of otitis media. Pseudomonas aeruginosa and Staphylococcus aureus were the most common causative microorganisms of ear infection. Keeping in view the importance of these pathogens, the present study had been designed to determine the sensitivity pattern of clinical isolates of otitis media. These isolates were collected from different hospitals and pathological laboratories of Karachi and their sensitivity against cefepime and amoxicillin were determined by using disk diffusion method. The results have shown that Pseudomonas aeruginosa was the most common causative microorganism of ear infection. Cefepime, a fourth generation cephalosporin appeared to be an effective antibiotic against Pseudomonas aeruginosa and Staphylococcus aureus.

Antimicrobial susceptibility pattern of clinical isolates of Pseudomonas aeruginosa isolated from patients of lower respiratory tract infections.

The present study was conducted to determine the antibiotic susceptibility pattern of Pseudomonas aeruginosa from sputum samples of lower respiratory tract infection patients admitted to different hospitals of Karachi. Most of the hospitals are hampered with high frequency of nosocomial infections generally caused by multiresistant nosocomial pathogen. Among Gram-negative pathogens Pseudomonas aeruginosa considered as most challenging pathogen. The objective of the study was to determine frequency of Pseudomonas aeruginosa from sputum samples and to find out susceptibility pattern against four antibiotics widely used for treatment. The sputum samples from 498 patients were collected consecutively between January 2010 and March 2011 and were cultured and identified. According to CLSI (Clinical Laboratory Standards Institute) guidelines antimicrobial susceptibility testing was performed by disc diffusion method. Pseudomonas aeruginosa were isolated from 24% (120/498) of the lower respiratory tract patient. A higher resistance to Pseudomonas aeruginosa isolate was observed with piperacillin/tazobactam and cefipime i.e. 42% and 40% respectively. Imipenem was found to be most effective antibiotic against Pseudomonas aeruginosa (76% sensitivity) but amikacin resistance was continuously increasing. In conclusion the frequency of Pseudomonas aeruginosa was also higher among lower respiratory tract infection patients with alarmingly high rate of resistance among widely used antibiotics. These findings focused on careful consideration for monitoring and optimization of antimicrobial use in order to reduce occurrence and spread of antimicrobial resistant pathogen.