Učinak pretkondicioniranja piperinom na farmakokinetiku peroralno primijenjenog marbofloksacina u štakora

The present study was carried out to evaluate the effect of piperine pre-conditioning on the pharmacokinetics of marbofloxacin in Wistar rats. Marbofloxacin was administrated at a dose rate of 5 mg/kg body weight alone, and along with piperine pre-conditioning at a dose of 10 mg/kg of body weight, orally for 5 days in Wistar rats. The mean values of the half-life (t1⁄2β), maximum drug concentration (Cmax) and area under the curve (AUC) were 1.19 ± 0.17 h, 2.71 ± 0.09 μg/mL and 12.25 ± 0.77 μg.h/mL, respectively, in piperine pretreated rats. The values were significantly higher than the values observed in rats administered with marbofloxacin alone (1.12 ± 0.31 h, 2.28 ± 0.20 μg/mL and 9.24 ± 0.59 μg.h/mL, respectively). The drug clearance (ClB) in piperine pretreated rats was 0.04 ± 0.02 L/h/kg, which was significantly lower than the clearance rate of the drug (0.53 ± 0.03 L/h/kg) in the animals administered with marbofloxacin alone. The study reveals that piperine has a significant effect on the pharmacokinetics of marbofloxacin, which may be due to an increase in the drug absorption and inhibition of elimination of the drug in rats.U ovom je radu istražen učinak pretkondicioniranja piperinom na farmakokinetiku marbofloksacina Wistar štakora. Marbofloksacin je apliciran u dozi od 5 mg/kg tjelesne mase peroralno, samostalno i nakon pretkondicioniranja piperinom u dozi od 10 mg/kg tjelesne mase peroralno tijekom 5 dana. U štakora tretiranih piperinom prosječne vrijednosti poluživota (t1⁄2β) bile su 1,19 ± 0,17 h, maksimalna koncentracija lijeka (Cmax) 2,71 ± 0,09 μg/mL, a površina ispod krivulje (AUC) 12,25 ± 0,77 μg.h/mL. Navedene vrijednosti bile su znakovito više od onih utvrđenih u štakora tretiranih samo marbofloksacin (1,12 ± 0,31 h, 2,28 ± 0,20 μg/mL i 9,24 ± 0,59 μg.h/mL). Klirens lijeka (ClB) u štakora tretiranih piperinom bio je 0,04 ± 0,02 L/h/kg što je bilo znakovito niže od klirensa lijeka (0,53 ± 0,03 L/h/ kg) u životinja koje su dobivale samo marbofloksacin. Ovo istraživanje pokazuje da piperin znakovito utječe na farmakokinetiku marbofloksacina, što može biti posljedica povećane apsorpcije lijeka i inhibicije uklanjanja lijeka u štakora

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR DETERMINATION OF HYDROCHLOROTHIAZIDE, OLMESARTAN MEDOXOMIL AND THEIR RELATED SUBSTANCES IN COMBINED TABLET DOSAGE FORM

Objective: Development of RP-HPLC method for determination of Hydrochlorothiazide (HCTZ), Olmesartan medoxomil (OLM) and their related substances in combined tablet dosage form and validation of the developed method. Methods: Gradient mobile phase system was used for estimation of drug contents and their related substances. Mobile phase A contained the mixture of Acetonitrile and 15 mM Phosphate buffer (pH adjusted to 3.4 with orthophosphoric acid) in the ratio of 20:80. Mobile phase B contained the same mixture in the ratio of 80:20. Chromatographic separation was carried out at the mobile phase flow rate of 0.8 mL/min using C18 Phenomenax inplace of Enable (250 × 4.6 mm) 5 μm column and detection was made at 254 nm. Results: The linearity of developed method was tested in the range of 62.5-187.5 μg/mL for Hydrochlorothiazide, 100-300 μg/mL for Olmesartan medoxomil, 1-1.8 μg/mL for Hydrochlorothiazide. The % recovery was found to be 99.88-100.67 % (HCTZ), 99.14-99.91 % (OLM), 99.11-100.71% (HCTZ-IMP) and 98.13-100.83% (OLM-IMP). The assay of marketed formulation was found to be 99.78% (HCTZ) and 99.26% (OLM). Conclusion: A simple, precise and accurate RP-HPLC method was developed for determination of Hydrochlorothiazide, Olmesartan medoxomil and their related substances

Farmakokinetika ceftriaksona u teladi

The pharmacokinetics of ceftriaxone was determined after a single intravenous and intramuscular administration at the dose rate of 10 mg/kg in crossbred cow calves. The drug concentration in plasma was quantified through High Performance Liquid Chromatography with UV detection. Following intravenous administration the drug was rapidly distributed (t1/2α: 0.13 ± 0.01 h; Vd(area); 0.44 ± 0.07 L/kg) and eliminated (t1/2β: 1.58 ± 0.06 h) from the body with a clearance rate of 3.15 ± 0.41 mL/min/kg. Following intramuscular administration, the peak plasma drug concentration (Cmax) was 15.34 ± 2.39 μg/mL at 0.25 hours (Tmax) suggesting very rapid absorption. The drug was extensively distributed (Vd(area): 1.16 ± 0.15 L/kg) and slowly eliminated (t1/2β: 5.02 ± 0.51 hours; Cl(B): 2.71 ± 0.29 mL/min/kg) following intramuscular administration. The absolute bioavailability of ceftriaxone was 47.0 ± 5.0% following intramuscular injection. However, it can be used at a dosage of 10 mg/kg intramuscularly, repeated at twelve-hourly intervals, for the treatment of susceptible bacteria infections in calves.Farmakokinetika ceftriaksona određivana je u križane teladi nakon njegove jednokratne intravenske i intramuskularne primjene u dozi od 10 mg/kg. Koncentracija lijeka u plazmi određivana je tekućinskom kromatografifi jom visokog učinka s UV zrakama. Raspodjela lijeka bila je brza nakon intravenske primjene (t1/2α: 0,13 ± 0,01 h; Vd(area): 0,44 ± 0,07 L/kg), a izlučivanje (t1/2β: 1,58 ± 0,06 h) iz tijela s klirensom od 3,15 ± 0,41 mL/min/kg. Nakon intramuskularne primjene vršna koncentracija u plazmi iznosila je (Cmax) 15,34 ± 2,39 μg/mL tijekom 0,25 sati (Tmax) što upućuje na vrlo brzu apsorpciju. Raspodjela lijeka bila je izrazito dobra (Vd(area) 1,16 ± 0,15 L/kg), a izlučivanje sporo (t1/2β: 5,02 ± 0,51 sati; Cl(B): 2,71 ± 0,29 mL/min/kg) nakon intramuskularne primjene. Apsolutna biološka raspoloživost nakon intramuskularne primjene ceftriaksona iznosila je 47,0 ± 5,0%. Međutim, on se može rabiti u dozi od 10 mg/kg i.m. te ponavljati u razmacima od 12 sati radi liječenja bakterijskih zaraza u teladi

Cadmium induced oxidative stress-mediated pathophysiological alterations in chickens and their amelioration by polyherbal mixture enriched feed

The study was conducted to evaluate sub-acute toxicity of cadmium (Cd) in broiler chickens and its amelioration by polyherbal mixture enriched feed (PHMEF). Thirty broiler chickens were divided into five groups. Chickens of group 1 were kept as control (C1). Chickens of group T1, T2, T3 and T4 were exposed to cadmium (as cadmium chloride) through drinking water (100 ppm), Vitamin C with Vitamin E (250 mg/kg each) in feed + Cd in drinking water (100 ppm), PHMEF (2%) alone, and PHMEF (2%) + cadmium in drinking water (100 ppm) for 28 days, respectively. Haematology, serum biochemical parameters, oxidative stress parameters like superoxide dismutase, catalase, reduced-glutathione and malondialdehyde, cadmium accumulation in organs like kidney, liver and thigh muscle, scanning electron microscopy (SEM) of ileum, and histopathological examination of kidney, liver and intestine were performed to evaluate toxicity of cadmium and ameliorating potential of PHMEF in broiler chickens. PHMEF modifies biochemical parameters, and oxidative stress markers. There was a significant reduction of cadmium accumulations in the PHMEF treated group.Polyherbal mixture enriched feed showed ameliorating effect against cadmium induced toxicity due to antioxidant effect as well as effect on accumulation of the cadmium in chicken

Pharmacokinetics and Dosage Regimen of Cefepimefollowing Single Dose Intravenous Administration in Calves

Pharmacokinetics of cefepimewas studied after single dose intravenous administration at the dose rate of 5 mg/kg body weight in calves. Blood samples were collected from the jugular vein at predetermined time intervals before and after drug administration. Serum was harvested and analysed for cefepimeconcentration by reverse-phase high performance liquid chromatography. Following intravenous administration, the mean serum cefepimelevel of 44.93 ± 5.47 μg/mL was observed at 0.033 h (2 minutes). The therapeutically effective concentration of cefepime(≥ 1.00 μg/mL) was maintained in serum up to 12 h. The distribution half-life (t1/2a) and elimination half-life (t1/2β) were 0.09 ± 0.01 hand 3.70 ± 0.16 h, respectively. The mean values of apparent volume of distribution [Vd(area)] and volume of distribution of drug at steady-state (Vd (ss)) were calculated to be 0.57 ± 0.03 and 0.43 ± 0.03 L/kg, respectively. The mean value of total body clearance (ClB) was 1.81 ± 0.16 mL/min/kg. The average values for area under serum drug concentration-time curve (AUC) and area under first moment of curve (AUMC) were 47.73 ± 4.05 μgh/mL and 190.3 ± 19.9 μg h2/mL. The average value of mean residence time (MRT) was 3.95 ± 0.11 h. A satisfactory intravenous dosage regimen would be 4.20 mg/kg body weight as priming dose followed by 3.78 mg/kg repeated at 12 h intervals

Evaluation of effects of <em>Opuntia elatior</em> Mill. fruit juice and quercetin on biochemical parameters and histopathological changes in diabetic rats

576-583The present study was carried out to evaluate safety profile following administration of Opuntia elatior Mill. fruit juice (OEFJ) and quercetin for 28 days in diabetic rats. OEFJ (4 mL/kg p.o. for 28 days) and quercetin (50 mg/kg p.o. for 28 days) treatment shown restoring effect on haemoglobin, packed cell volume and total erythrocyte count in diabetic rats. Alterations in levels of alanine aminotransferase, creatinine, total bilirubin and lactate dehydrogenase observed in diabetic rats which were restored to normal level when diabetic rats were treated with OEFJ and quercetin alone and in combination. The mean values of total protein, albumin, globulin, total bilirubin, BUN and ALP were found unaltered in all groups. Damage induced by streptozotocin in pancreas, liver and kidney were lesser compared to diabetic control group when rats were treated with OEFJ and quercetin. However, no appreciable histopathological lesions have been observed in the spleen, heart, lung and intestine of rats in all treatment groups. In conclusion, Opintia elatior Mill. fruit juice have shown protective effect against alterations in biochemical parameters and pathological lesions of pancreas and liver in diabetic rats

Safety level of Levofloxacin following repeated oral adminstration in White Leg Horn&amp;#160;layer birds

Levofloxacin is a fluorinated quinolone which has broad-spectrum antibacterial activity at low plasma/tissue concentration. The present study was designed to investigate safety of levofloxacin (10 mg/kg) after repeated oral administration at 12 hours interval for 14 days in layer birds (30-35 weeks old and weighing between 1.5-2.0 kg) and to determine tissue concentration of the drug following oral administration (10 mg/kg) for 5 days. Drug concentration in tissue was determined using High Performance Liquid Chromatography (HPLC). Repeated oral administration of levofloxacin in layer birds was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC), blood biochemical (AST, ALT, AKP, ACP, LDH, BUN, Serum total protein, Serum albumin, Serum Creatinine, Blood glucose and Total bilirubin) and histopathology of liver, kidney and joint cartilage. Levofloxacin could not be detected in body tissues (liver and skeletal muscle) at 12 hours after the last administration. [Vet. World 2009; 2(4.000): 137-139