Assessment of potential interaction between simvastatin and clarithromycin in healthy adult male subjects

Cardiac patients with weak immune system are susceptible to bacterial infections. Their prescriptions frequently contain simvastatin and clarithromycin together. The objective of present project was to assess the potential interaction between simvastatin and clarithromycin by evaluating the clarithromycin effects on the pharmacokinetics of simvastatin in healthy adult male subjects. The study design comprised of two phases, used at interval of one week. In first phase simvastatin 20 mg alone was administered to each volunteer. In second phase, co-administration of simvastatin 20 mg with clarithromycin 250 mg was made under similar specified conditions. Blood samples were collected at specified time intervals. Simvastatin plasma concentrations were analyzed through High Performance Liquid Chromatography with UV detector at 238 nm wavelength. Using one compartment open model, MW/PHARM version 3.02 software program was used by F. Rombut for pharmacokinetic parameters calculation. Clarithromycin co-treatment resulted in 2.3 fold increase in maximum plasma concentration Cmax [from 2.47 +/- 0.34 ng.mL-1 to 5.66 +/- 1.18 ng.mL-1; p<0.05] and 3.9 fold increase in area under time versus concentration curve from 0 to 10 hours AUC0-10 [from 15.10 +/- 3.73 ng.hr.mL-1 to 58.49 +/- 15.73 ng.hr.mL-1; p<0.05] of simvastatin. These results suggest that co-prescription of simvastatin and clarithromycin should be avoided to minimize the adverse events resulting from high simvastatin concentration, without sacrificing therapeutic worth of simvastatin

Disposition kinetics of omeprazole in healthy female volunteers in Pakistan

Omeprazole [OMP] a proton pump inhibitor is widely used to suppress gastric acid secretions of parietal cells of stomach and metabolized predominantly by CYP2C19. The objective of the present study was to investigate the pharmacokinetics and dosage regimen of OMP, after its single oral administration in eight healthy adult female subjects. Blood samples were collected at different time intervals after oral administration and their pH was measured. Plasma concentration of OMP was determined by high performance liquid chromatography [HPLC] system equipped with UVvisible Detector. The concentration versus time data was used to compute the pharmacokinetic parameters with the help of computer software programme MW/PHRAM APO version 3.02.Peak plasma concentration was [Cmax] 0.38 +/- 0.04 microg/ml achieved at 2.07 +/- 0.22 hrs. The elimination half-life [t1/2beta] was1.82 +/- 0.42 hrs. Volume of distribution [Vd] in the present study was 0.40 +/- 0.07 l/kg with total body clearance [ClB] 0.19 +/- 0.02 l/hr/kg and area under the curve [AUC] 1.89 +/- 0.23 microg.hr/ml. The pharmacokinetic properties which are different from the literature after oral administration of 20 mg OMP in eight healthy female volunteers may be due to the variations of environment and genetic variation between Pakistan and drug manufacturing of foreign countries

Histopathological evaluation of gastro protective effect of Berberis vulgaris [Zereshk] seeds against aspirin induced ulcer in albino mice

The present study was carried out to investigate the antiulcer activity of Berberis vulgaris [Zereshk] seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300mg/kg, 600mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced thetissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris [900mg/kg] showed similar results as synthetic antiulcer drug omeprazole

Cefixime; disposition kinetics and bioavailability comparison of two formulations of cefixime in healthy adult male subjects

Cefixime is a third generation and orally acting cephalosporin. It is a cell wall synthesis inhibitor and is well stable to presence of beta lactamase enzymes. Environmental and genetic differences play a greater role in disposition kinetics of a drug. To determine disposition kinetics of cefixime in local population and to evaluate the bioequivalence of multinational and national brands of cefixime. 2013-2014. Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad. In present study disposition kinetics and bioequivalence of two brands of cefixime, cefspan and ceforal-3, were investigated in 10 adult healthy male subjects after a single oral dose of 400 mg capsule of each with a 7 days washout period. After blood sampling, plasma concentration of cefixime was determined by HPLC method. For computing disposition kinetic parameters, one compartment open model was applied. Mean values of disposition kinetic parameters; t1/2 Beta 5.01 and 4.72 hours, Vd 1.10 and 1.29 L/kg and CI[B] 0.16 and 0.21 L/hr/kg of cefspan and ceforal-3, respectively, were found non significantly [P 0.05] different. Similarly mean values of bioavailability parameters; AUC 36.58 and 32.99microg.hr/mL, AUMC 282.95 and 264.13 microL/g.hr[2]/mL and MRT 7.79 and 7.83 hours of cefspan and ceforal-3, respectively, remained non significantly [P > 0.05] different. All the parameters were compared by paired t-test. Relative bioavailability was found to be within the range 80-125% which is acceptable for bioequivalence. The test formulation, ceforal-3, was found bioequivalent to the reference formulation, cefspan

Pharmacokinetic studies of metformin and glibenclamide in normal human volunteers

The study was aimed to evaluate various pharmacokinetic parameters of a commercially available fixed dose combination of oral antidiabetics [Metformin/Glibenclamide 500/5mg tablets] in plasma sample of normal healthy adult male volunteers by applying an accurate, selective, and reproducible HPLC-UV analytical method for quantification of Metformin HCL and Glibenclamide simultaneously in a single chromatographic run. Previously no HPLC-UV analytical method for simultaneous estimation of Metformin/Glibenclamide has been reported in Pakistan. The human plasma samples were evaluated by using an isocratic High Performance Liquid Chromatography [HPLC] system of Sykam consisted of a pump with a column of Thermo Electron Corporation USA [ODS hypersil C[18] 4.6 mm x 250 mm], a UV-detector with data processing Clarity software. The mobile phase of 0.040M Potassium dihydrogen phosphate containing 0.25mL/L triethylamine at pH 3.5 [adjusted with 1:1 phosphoric acid] and acetonitrile [465: 535v/v] was delivered with injection volume of 100microL at flow rate of 1 mL/min at 25degreeC temperature. The detection was performed at lamda[max]230 nm. By applying this method, important pharmacokinetic parameters C[max], T[max], AUC[0-infinity], AUMC[0-infinity], t[1/2], Ke, MRT, V[d] and Cl[T] are calculated. Maximum plasma concentrations C[max] was 131.856 +/- 8.050ng/ml for Glibenclamide [Mean +/- SEM] and 511.106 +/- 12.675 ng/ml for Metformin HCl [Mean +/- SEM].

Lipid lowering effect of Cinnamomum zeylanicum in hyperlipidaemic albino rabbits

The purpose of the present study was to investigate the lipid lowering effect of Cinnamomum zeylanicum [Cinnamon] in hyperlipidaemic albino rabbits. For this purpose, forty eight albino rabbits were randomly divided into eight equal groups; untreated control on normal routine feed, untreated control on butter and cholesterol, treated control on synthetic cholesterol lowering drug simvastatin [Tablet survive[R] 20 mg], three treated groups on three respective doses of C. zeylanicum bark powder and two treated groups on water and methanol extracts of C. zeylanicum bark powder. Butter ad lib and cholesterol powder 500 mg/kg body weight were used to induce experimental hyperlipidaemia in all groups except untreated control group. The results suggested that C. zeylanicum bark powder at the rate of 0.50 g/kg, 0.75 g/kg and methanol extract equivalent to 0.75 g/kg powder produced respective percent reductions in total lipids by 45, 49 and 64; triglycerides by 38, 53 and 60; total cholesterol by 53, 64 and 69 and LDL-cholesterol by 50, 59 and 62. However, at these dosage levels HDL-cholesterol showed respective percent increase of 42, 48 and 53. Nonetheless, C. zeylanicum bark powder at the level of 0.25 g/kg and C. zeylanicum extract in water could not significantly reduce lipid profile indicators. Based on these studies, it can safely be said that C. zeylanicum bark powder methanol extract equivalent to 0.75 g/kg bark powder and simvastatin [0.6 mg/kg b. wt.] were equieffective in treating hyperlipidaemia

Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers

Carbamazepine is a [CYP1A2 and CYP3A4 enzyme inducer] medicine which is used by epileptic patients for a long time. During the course of therapy, patients are generally caught by other diseases like urinary tract infections, upper respiratory tract infection, skin and soft tissue infection etc. To cure them, physicians commonly prescribe fluoroquinolones like Ciprofloxacin [CYP1A2 inhibitor] along with Carbamazepine [CBZ]. Interactions may result without recognition which may lead to unforeseen toxicity, untoward effects or even therapeutic failure. Therefore, studies were conducted to investigate the effect of Ciprofloxacin on the pharmacokinetics of Carbamazepine in healthy adult male volunteers. The main objective of this study was to generate new knowledge regarding CBZ and Ciprofloxacin interaction for physicians and research workers dealing with these medicines. Eight healthy adult male volunteers were selected to assess the effect of ciprofloxacin on the pharmacokinetics of Carbamazepine. After overnight fast the selected male volunteers were given CBZ orally. Blood samples were drawn at different time intervals after medication. Then the same volunteers were given CBZ along with ciprofloxacin. Blood samples were again drawn at the same time intervals as done previously. Plasma was separated from the blood samples. Concentration of CBZ in the plasma samples was determined by using HPLC technique. Results of the present study indicated that ciprofloxacin significantly increased the plasma concentration of CBZ when given concurrently to the healthy adult male volunteers. Ciprofloxacin increased C[max], AUC and t [1/2] while it decreased the CL and Vd of CBZ when administered concurrently to the adult volunteers. Change in pharmacokinetic parameters was due to slow metabolism or elimination of CBZ when given concurrently with ciprofloxacin to the adult volunteers. This is probably due to the inhibition of CYP3A4 isoenzyme by ciprofloxacin which is responsible for metabolism of CBZ. Ciprofloxacin increased the plasma concentration of CBZ so dose adjustment as well as drug monitoring of CBZ is required when both the drugs are given concurrently. The knowledge regarding interaction between ciprofloxacin and CBZ would be helpful for the pharmaceutical industries, physicians and a blessing for the patients

Pharmacokinetics and dosage regimen of ciprofloxacin following single intramuscular administration in Teddy goats

The objective of this study was to determine the pharmacokinetics and dosage regimen of ciprofloxacin in Teddy goats. Ciprofloxacin was administered intramuscularly at 5 mg/kg body weight in each of eight animals. Following drug administration, blood samples were collected at different time intervals and analyzed for ciprofloxacin using HPLC. Pharmacokinetic parameters were calculated using two compartment open model. Peak plasma concentration [C[max] of ciprofloxacin, 1.77 +/- 0.20 microg/ml was achieved at 0.90 +/- 0.04 hours [T[max]. Values for half-life of absorption [t [1/2] abs], distribution [t [1/2] alpha] and elimination [t [1/2] beta] were 0.52 +/- 0.04, 0.52 +/- 0.04 and 2.62 +/- 0.39 hours, respectively. The value for apparent volume of distribution [Vd] was 3.76 +/- 0.92 1/kg, area-under-the-curve [AUC] 5.89 +/- 0.91 microg.hr/ml and total body clearance [CL] was 1.09 +/- 0.11 1/hr/kg. Based on these results, it was concluded that calculated dose should be higher than the dose recommended by the manufacturer to treat susceptible bacteria in goats

Comparative efficacy of fumaria parviflora and morantel tartrate against mixed gastrointestinal nematode infection in sheep

Faecal eggs per gram [EPG] counts were determined before and after administration of powdered whole plant of Fumaria parviflora, Lam. in 0.5, 1 and 2 g/kg body weight doses in the sheep suffering from mixed gastrointestinal nematode infection. Non-significant reduction of EPG counts were produced on post-treatment days 3rd, 10th and 15th at 0.5 g/kg body weight. However, in 1 and 2 g/kg body weight doses EPG values were significantly [P<0.05 or 0.001] reduced on days 10 and 15. The water and ethanol extracts of F. parviflora equivalent to 2 g/kg of the crude powder were.also administered orally to the infected sheep. The water extract could not significantly reduce the EPG counts on all post-treatment days checked. However, the ethanol extract produced a highly significant decrease in EPG values on days 10 and 15. Morantel tartrate [0.01 g/kg] produced a highly significant reduction of EPG counts in the treated sheep. These data suggested that 2 g/kg of F. parviflora and its equivalent ethanol extract and Morantel tartrate [0.01 g/kg] are equipotent in treating the sheep suffering from natural mixed gastrointestinal nematode infection