RESUMO
The alarming rise in the rate of multi drug resistant, life threatening gram negative infections has brought renaissance in the use of Colistin for last two decades. The major constraint in its utilization is its nephrotoxicity. Therefore it is being underused which is favoring the development of resistance. This study assesses the prevention of nephrotoxicity associated with high and low toxic doses of Colistin by alpha-tocopherol. Thirty rabbits were randomly divided into five groups. Baseline serum urea, creatinine and electrolytes were estimated. A loading dose of colistin was given in the form of infusion followed by I.M injections for six days. In the preventive groups alpha-tocopherol was additionally given orally for two weeks. Rabbits were sacrificed 24 hours after the last dose. The kidney slides graded and statistically analyzed using [chi square]. The results of serum analysis were compared using one way analysis of variance followed by post hoc tukey test. There was marked nephrotoxicity in high toxic group where as in low toxic group mild nephrotoxicity was evident. Alpha-tocopherol attenuated the renal insult in both the toxic groups. As damage induced by colistin is oxidative in nature, thus it was concluded that the protection offered by alpha- tocopherol is due to its antioxidant activity
RESUMO
Objective: To obtain pharmacokinetic data of Orvastin, a newly launched formulation of atorvastatin, in healthy males of Pakistan
Study Design: It was quasi-experimental design
Place and Duration of Study: Study was conducted at Centre for Research in Experimental and Applied Medicine [CREAM] Army Medical College, Rawalpindi and duration of study was about ten months
Material and Methods: Twenty-four healthy male subjects were taken conveniently from Pakistani population. Two tablets of Orvastin, each containing atorvastatin 40mg, were administered orally as a single dose. Multiple blood samples were taken with small gaps in between up to the period of 48hrs. High Performance Liquid Chromatography [HPLC] with UV-detector was used for quantification of atorvastatin in plasma; wavelength of UV-detector was adjusted at 247nm. Mobile phase was made up of 60 percent acetonitrile and 40 percent 0.05M sodium phosphate buffer. Flow rate of mobile phase was maintained at 1.5ml/min with 5.5 pH. Progesterone was used as an internal standard. Stock solutions of atorvastatin were made by dissolving it into methanol and acetonitrile was used for making stock solution of progesterone. Calibration curves were made for atorvastatin and internal standard from concentration time data, values for time to achieve maximum plasma concentration. [Tmax] and maximum plasma concentration [Cmax] were directly calculated. Computer program [APO, MW PHARM, and Ver. 3.60] was used for calculation of pharmacokinetic profile of atorvastatin
Results: Atorvastatin was detected in plasma samples of all volunteers. The absorption rate constant [Ka] was 0.41 l/hr. Cmax was 26.69 +/- 6.67 micro g/l and Tmax was 3.33 +/- 0.41 hrs. Apparent volume of distribution [Vd], of atorvastatin, was 3244.84 +/- 1237.36 liters. The elimination rate constant was 0.15 l/hr. Elimination half-life of atorvastatin was 6.14 hours. Trapezoidal rule was used for calculation of AUC[0-48] and AUC[0-infinity] and it was found to be 208.77 h/micro g/l and 208.74 h/micro g/l respectively. Clearance of atorvastatin was 420.87 +/- 170.64 liters/hour and Mean Residence Time [MRT] was 8.86 +/- 5.01 hours
Conclusion: Pharmacokinetic data of new formulation of atorvastatin is in comparable range with other brands of atorvastatin used in different ethnic groups