Pharmacokinetic and drug interaction studies of Pefloxacin with paracetamol [NNAID] in healthy volunteers in Pakistan

In the present study, the pharmacokinetic and drug interaction evaluation of two drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment and two-sequence crossover design. Total fifteen healthy volunteers participated out of which ten completed the study. All were male volunteers, aged 22.36 years [means], with a mean weight of 76.45 +/- 12.05 Kg. The washout period between treatments was 5 week. Initially the method utilized for quantitative analysis of the drug was developed which was further validated. The study involved plasma protein precipitation with ethyl acetate and detection was done at 275nm. The retention time for pefloxacin 18 +/- 1 min and paracetamol were approximately 6 +/- 1 min, respectively. The calibration curve for pefloxacin was linear in the concentration range of 0.125-12.0 micro g/ml with r[2]=0.9987 in plasma. Standard concentration solution was maintained on the same temperature as that of volunteer's samples to optimize the periods for the determination of drug concentration in the plasma samples. Blood samples were collected from volunteers at different time intervals. The pharmacokinetics and drug interaction studies were anticipated by plotting concentration versus time-profiles. The value of AUC[0-infinity] in control was 67.355 +/- 3.174 micro g.h/ml, in treatment 61.242 +/- 3.868 micro g.h/ml along with relative bioavailability =91.395 +/- 4.864. Under the control and treatment condition the mean maximum plasma concentrations were found to be 4.679 +/- 0.248 micro g/ml and 4.6595 +/- 0.266 micro g/ml respectively. The average T[max] for plasma concentrations was 1.819 +/- 0.1743hr and 1.605 +/- 0.1134hr respectively. The biological half-lives in the two phases of studies were found to be 7.953 +/- 0.33hr in control and 7.7257 +/- 0.355hr in treatment. No significant effect were observed on the bioavailability and pharmacokinetics of pefloxacin by the concomitant administration with paracetamol, however very minor effect were observed that might be related with inter-individual variation in human volunteers. This pharmacokinetic studies also indicated that the level of drug [Cmax] do not differ from previous studies in different races

Anti-inflammatory and analgesic activities of ethanolic extract of sphaeranthusindicus linn

The aim of the present study was to evaluate the intensity of the anti-inflammatory and analgesic activities of Sphaeranthus indicus on albino mice and rat of either sex. The flowers of S. indicus are an important herb used in folk eastern medicines. In this study, the ethanolic extract of S. indicus in doses of 300 and 500 mg/kg was used. Anti-inflammatory activity was evaluated by measuring the mean decrease in hind paw volume after the sub planter injection of carrageenan. The analgesic activity was tested against acetic acid induced writhing response using albino rats. Result of the study shows that at the end of one hour the inhibition of paw edema was 42.66 and 50.5% respectively and the percentage of protection from writhing was 62.79 and 68.21 respectively. S. indicus possesses several important pharmaceutical and pharmacological properties. The current study describes that flower of S. indicus has significant anti-inflammatory and analgesic properties. Conclusion of the study is that this herbal medicine can be used as an alternative therapy for the treatment of minor to moderate types of inflammation and as a painkiller

Antimicrobial susceptibility testing of newer quinolones against gram positive and gram negative clinical isolates

Antibiotic resistance development is an ongoing process associated with irrational antibiotic use. WHO recommends regular surveillance programs for monitoring of antibiotic resistance. The present study is a step in this direction. A total of 124 clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different hospitals in Karachi. In vitro antimicrobial susceptibility studies were carried out by agar dilution method using newer quinolones that included Gatifloxacin and Levofloxacin. It was observed that 50% [n=30] isolates of Staphylococcus aureus were resistant to gatifloxacin. Gatifloxacin was more active against Pseudomonas aeruginosa [n=23] and showing complete susceptibility with MIC 1mg/L except for three very resistant strains that shown resistance at even higher concentrations. Escherichia coli [n=45] has shown 15.5% and Klebsiella pneumoniae [n=26] 34.61% resistance to gatifloxacin. Levofloxacin was more active against Staphylococcus aureus and Escherichia coli showing complete susceptibility at 0.5 mg /L concentration. Pseudomonas aeruginosa and Klebsiella pneumoniae were found to be resistant to Levofloxacin showing 36.36% and 23.08% resistance respectively. The study strongly recommends the adherence to the antibiotic policy and regular susceptibility testing to overcome the problem associated with antimicrobial resistance

Development of new ophthalmic suspension prednisolone acetate 1%

Formulation of a new Prednisolone acetate [1%] ophthalmic suspension to obtain a better contactibility of the drug at the site of action. The formulation was evaluated and optimized based on physiological, physicochemical and pharmaceutical parameters and prepared aseptically, keeping particle size between 1-3 micro m, while viscosity enhancer, preservative, chelating agent were used to increase the transient residence time, antimicrobial preservation respectively. Isotonicity of the formulation was maintained. Buffering agents used were having buffering capacity NMT 0.05%. pH adjusted at which Prednisolone acetate was stable. The finished product subjected to stress conditions to check the physical stability of the formulation. The formulation was packed in LDPE plastic vials, and subjected to accelerated stability studies at 40°C and the kinetic and predictive method was employed for the determination of degradation rate constant and shelf life. The results showed that the development of a new ophthalmic formulation having significantly better contact time by the selection and optimization of viscosity [HPMC] that obtained [21 cps] with better stability studies. The results concluded that prednisolone acetate 1.0 per cent ophthalmic suspension is more effective than prednisolone phosphate 1.0 per cent ophthalmic solution in suppressing corneal inflammation

Development and validation of a HPLC method for determination of pefloxacin in tablet and human plasma

Developing and validating a simple, efficient, reproducible and economic reversed phase high performance liquid chromatographic [RP-HPLC] method for the quantitative determination of pefloxacin in bulk material, tablets and in human plasma. A shim-pack CLC-ODS column and a mobile phase constituting acetonitrile: 0.025 M phosphoric acid solution [13:87 v/v, pH 2.9 adjusted with KOH] was used. The flow rate was 1 ml/min and the analyses performed using ultraviolet [UV] detector at a wavelength of 275 nm using acetaminophen as an internal standard. The developed method showed good resolution between pefloxacin and acetaminophen. It was selective to pefloxacin and able to resolve the drug peak from internal standard and from formulation excipients. The percentage of coefficient variation [CV] of the retention times and peak areas of pefloxacin from the six consecutive injections were 0.566% and 0.989%, respectively. The results showed that the peak area responses are linear within the concentration range of 0.125 mg/ml-12 mg/ml [R2=0.9987]. The limits of detection [LOD] and limits of quantitation [LOQ] for pefloxacin were 0.03125 mg/ml and 0.125 mg/ml. The intra-day and inter-day variation, RSD were 0.376-0.9056 and 0.739-0.853 respectively; also, inter-day variation with relative standard deviation [RSD] were 0.1465-0.821 in plasma. The accuracy results of 70%, 100%, and 130% drugs were 100.72%, 100.34%, and 100.09%, respectively. The method is linear, quantitative, reproducible and could be used as a more convenient, efficient and economical method for the trace analysis of drug in biological fluids, in raw material and tablets

Product management and efficacy evaluation of an anti-coagulant Enoxaparin [Clexane] in Pakistan

Enoxaparin [Clexane] is a low molecular weight heparin with a molecular weight of around 4500 D. It is a blood thinner used to treat pulmonary embolism, Deep vein thrombosis, unstable angina, non-ST elevated myocardial infarction and ST- segment elevation myocardial infarction. This project is designed to evaluate the most widely used Low molecular weight heparin [LMWH], enoxaparin in patients with Acute Coronary Syndrome [ACS] based on prescriptions evaluation. Prescriptions were collected from different health institutes and were evaluated on the basis of Market Share, MIP data-competitors, MIP data-indication, and on MIP data-specialty. The study included both male and female patients of age ranging between 50-70 years. The results reflect the prescription patterns of enoxaparin [Clexane] by evaluating 73 prescriptions from major cardiovascular hospitals in Pakistan between February 2008 and October 2008. The prescription pattern showed that physicians in Pakistan have a tendency of prescribing enoxaparin with other drugs. The results also showed that patients were prescribed multiple anti-coagulants concomitantly, including enoxaparin and aspirin. Overall, the analysis of anti-coagulants has indicated that enoxaparin is the drug of choice for the treatment of ACS

Paediatric nosocomial infections: resistance pattern of clinical isolaten

Hospital acquired infections are transmitted to patients by hospital personnel and other patients, or they may arise from patient's own endogenous flora. Children are one of the most susceptible subjects associated in the hospitalacquired infections and have a higher prevalence rate for infections. This problem is at its extremes in developing countries like Pakistan where in most of cases the severity depends on the hygienic conditions of the Hospitals and lack or lapse of infection control measures. To have a surveillance type of data in this regard, one hundred and twenty four isolates of Pseudomonas aeruginosa/Pseudomonas species, Staphylococcus aureus [MRSA/MSSA] and Klebsiella species, that are commonest among the nosocomial infection causing organisms, were collected from pediatric hospital settings in Karachi. A study of incidence and resistance pattern by Kirby Baur disc diffusion method, with selected antimicrobials, was carried out. These isolates were resistant against most antimicrobials tested. Drugs like mmipenem, meropenem, amikacin, vancomycin [especially in MRSA or BRSA], Fucidic acid [for burns and other infections] and some of the 3rd generation cephalosporins were found quite effective