Pharmacokinetic study of atorvastatin after single dose administration among Pakistani population

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

Protective effect of pioglitazone on gentamicin induced nephrotoxicity in rabbits

Objective: To evaluate potential role of pioglitazone in protecting kidneys from nephrotoxic insult produced by Gentamicin

Study design: Comparative study on animal model

Place and Duration of Study: Department of Pharmacology Army Medical College, duration of study was six months

Material and Methods: Twenty four rabbits were randomly divided into four groups [n=6]. Group [Gp]-1 received 1 milliliter [ml] isotonic saline intraperitoneally [IP] daily for 13 days. Gp-2 received gentamicin 40 miligram/kilogram/day [mg/kg/day] IP daily for 13 days. Gp-3 received pioglitazone salt 10 mg/kg/day dissolved in drinking water via feeding tube for 13 days. Gp-4 received pioglitazone salt 10 mg/kg/day via feeding tube plus gentamicin 40 mg/kg/day IP for 13 days. Blood was collected on days 0 and 14 for estimation of serum urea and creatinine. All animals were sacrificed and kidneys were removed for renal histological examination

Results: Pioglitazone did not show any nephroprotective effect against gentamicin induced nephrotoxicity

Conclusion: Pioglitazone fails to exhibit nephroprotective potential when administered along with nephrotoxic dose of gentamicin

Protective effect of metformin against gentamicin induced nephrotoxicity in rabbits

Gentamicin is used against gram negative infections, but major problem encountered is nephrotoxicity that occurs in 10-20% of therapeutic regimes. Gentamicin induced oxidative stress plays an important role in this nephrotoxicity. Recent data has shown metformin to possess antioxidant activity. Purpose of study was to evaluate potential role of metformin in protecting kidney from nephrotoxicant insult. Thirty-six rabbits were randomly divided into six groups [n=6]. G-1 received 1 ml isotonic saline intraperitoneally [IP] daily for 13 days. G-2 received gentamicin [150 mg/kg/day] IP for last 6 days of 13 days. G-3 received gentamicin [40 mg/kg/day] IP for 13 days. G-4 received metformin salt [100 mg/kg/day] dissolved in drinking water via feeding tube for 13 days. G-5 received metformin salt [100 mg/kg/day] via feeding tube for 13 days plus gentamicin [150 mg/kg/day] IP for last 6 days of 13 days. G-6 received gentamicin [40 mg/kg/day] IP plus metformin salt [100 mg/kg/day] via feeding tube for 13 days. Blood was collected on days 0 and 14 for serum urea and creatinine estimation. All animals were sacrificed and kidneys were removed for renal histological examination. Metformin showed nephroprotective effect. It blunted nephrotoxic insult at 150 mg/kg/day of gentamicin, whereas showed complete nephroprotection at 40 mg/kg/day of gentamicin. Metformin offers complete nephroprotection at low toxic dose ranges of gentamicin. This could offer an efficacious and cheaper treatment alternative in those diabetics who also suffer from gram-negative infections

Prunes and liver function: a clinical trial

Prunes are used by folks as a remedy of various diseases including hepatitis. A clinical trial was designed to see the effects of prunes [Prunus domestica] on liver function. 166 healthy volunteers were divided into three groups randomly. Either three [about11.43g] or six [23g approx.] prunes were soaked in a glass of water [250ml] overnight. Each subject from two test groups was asked to drink prune juice and eat whole fruit[single or double dose of prunes] as well, early in the morning, daily for 8 weeks; whereas each subject from control group was given a glass of water to drink. Blood samples were taken at week 0 and week 8 for chemical analysis. There was significant reduction of serum alanine transaminase [p 0.048] and serum alkaline phosphatase [p 0.017] by the lower dose of prunes. There was no change in serum aspartate transaminase and bilirubin. Alteration in liver function by use of prunes may have clinical relevance in appropriate cases and prunes might prove beneficial in hepatic disease

Use of prunes as a control of hypertension

Fruits and vegetables are shown to reduce blood pressure. It is not merely the antioxidants contained in fruits and vegetables that have health benefits such as lowered systolic and diastolic blood pressures. This study was undertaken to see the cardiovascular protective effects of prunes. A placebo controlled clinical trial study was designed to see the effects of Prunus domestica on blood pressure in 259 pre-hypertensive [Systolic BP=120-139 mmHg, diastolic BP=80-89 mmHg] volunteers. Treated groups drank prune juice and ate the whole fruit [dried plums] while either 3 [about 11.5 gm] or 6 prunes were soaked overnight in a glass of water whereas control group took only a glass of plain water early in the morning on empty stomach. Blood pressure was recorded fortnightly for 8 weeks, and blood samples were taken at 0 and 8 weeks. There was significant reduction of blood pressure by single dose of prunes daily group and the controls [p<0.05]. With the double dose of prunes, only systolic BP was reduced significantly [p<0.05]. Control group had significantly increased serum HDL whereas test groups had significantly reduced serum cholesterol and LDL [p<0.05]. Data was analysed by paired-sample t-test with 95% confidence interval. The data predicts cardiovascular protective effects of prunes