Feed restriction is a common practice to reduce post weaning digestive disorders in rabbits and to get carcasses with less fat. Hydric restriction is commonly used to induce feed restriction in growing rabbits. Two hy...Feed restriction is a common practice to reduce post weaning digestive disorders in rabbits and to get carcasses with less fat. Hydric restriction is commonly used to induce feed restriction in growing rabbits. Two hydric restriction times (2 h and 4 h per day, continuously) were used in our trial carried in good sanitary conditions. Thirty six rabbits were divided at weaning (28 days) into three groups: R2 with restricted access to drinking water from 35 days to 80 days age of 2 h per day (from 8 a.m. to 10 a.m.), R4: access to drinking water 4 h per day (from 8 a.m. to 12 a.m.) and T (control group) with unlimited access to drinking water. Six animals from each group were slaughtered at 80 days of age. Carcass measurements and meat quality were studied. Histological study for kidneys was carried out. Relative weight of gastrointestinal tract increases with the degree of restriction: 16.5, 18.4 and 18.9 for T, R4 and R2, respectively (P 〈 0.05). Perirenal fat was lower in restricted groups but differences were not statically significant. Scapular fat decreases of 2/3 or 1/3 respectively with limiting access to drinking water of 2 h or 4 h per day. Compared to control group (T), meat of restricted groups contains more water: 70.3%, 70% and 69.3% respectively for R4, R2 and T (P 〈 0.01). The same tendency was observed for proteins: 19.2%, 19.3% and 17.7% for groups R2, R4 and T. Fat decreases in meat of restricted animals: 8.4%, 8.2% and 8.1% respectively for T, R4 and R2 (P 〈 0.05). Water restriction induced decrease of carcass and meat adiposity. There were no differences between pH post mortem and pH ultimate (after 24 h) between the three groups. Hydric restriction does not effect on kidney histology.展开更多
A liquid chromatography with tandem mass spectrometry(LC-MS/MS) method has been developed and validated for the measurement of sunitinib in rabbit plasma. After protein precipitation with acetonitrile, samples were ...A liquid chromatography with tandem mass spectrometry(LC-MS/MS) method has been developed and validated for the measurement of sunitinib in rabbit plasma. After protein precipitation with acetonitrile, samples were analyzed on a Zorbax Extend-C18 column(150 mm×4.6 mm, 5μm). The mobile phase consisted of a mixture of acetonitrile and deionized water(containing 0.05% formic acid) at a ratio of 27:73(v/v), and the flow rate was set at 0.8 mL /min. The column temperature was maintained at 30 oC. The LC eluate was detected by an electrospray ionization(ESI) source operated in the positive ion mode, and quantification was conducted using MRM of the transitions m/z 399.24→283.01 and m/z 415.19→178.00 for sunitinib and internal standard(IS, diltiazem hydrochloride), respectively. The calibration curve was linear in the range of 2–600 ng/m L. The lower limit of quantification was 2 ng/mL. The method also exhibited satisfactory results in terms of sensitivity, specificity, accuracy(with relative error ranging from –4.0% to 1.1%), precision(with intra- and inter-day relative standard deviations ranging from 2.8% to 9.5%), matrix effect, recovery as well as stability. Taken together, our newly developed method was reliable to monitor sunitinib concentrations in rabbit plasma.展开更多
OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the p...OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.展开更多
文摘Feed restriction is a common practice to reduce post weaning digestive disorders in rabbits and to get carcasses with less fat. Hydric restriction is commonly used to induce feed restriction in growing rabbits. Two hydric restriction times (2 h and 4 h per day, continuously) were used in our trial carried in good sanitary conditions. Thirty six rabbits were divided at weaning (28 days) into three groups: R2 with restricted access to drinking water from 35 days to 80 days age of 2 h per day (from 8 a.m. to 10 a.m.), R4: access to drinking water 4 h per day (from 8 a.m. to 12 a.m.) and T (control group) with unlimited access to drinking water. Six animals from each group were slaughtered at 80 days of age. Carcass measurements and meat quality were studied. Histological study for kidneys was carried out. Relative weight of gastrointestinal tract increases with the degree of restriction: 16.5, 18.4 and 18.9 for T, R4 and R2, respectively (P 〈 0.05). Perirenal fat was lower in restricted groups but differences were not statically significant. Scapular fat decreases of 2/3 or 1/3 respectively with limiting access to drinking water of 2 h or 4 h per day. Compared to control group (T), meat of restricted groups contains more water: 70.3%, 70% and 69.3% respectively for R4, R2 and T (P 〈 0.01). The same tendency was observed for proteins: 19.2%, 19.3% and 17.7% for groups R2, R4 and T. Fat decreases in meat of restricted animals: 8.4%, 8.2% and 8.1% respectively for T, R4 and R2 (P 〈 0.05). Water restriction induced decrease of carcass and meat adiposity. There were no differences between pH post mortem and pH ultimate (after 24 h) between the three groups. Hydric restriction does not effect on kidney histology.
文摘A liquid chromatography with tandem mass spectrometry(LC-MS/MS) method has been developed and validated for the measurement of sunitinib in rabbit plasma. After protein precipitation with acetonitrile, samples were analyzed on a Zorbax Extend-C18 column(150 mm×4.6 mm, 5μm). The mobile phase consisted of a mixture of acetonitrile and deionized water(containing 0.05% formic acid) at a ratio of 27:73(v/v), and the flow rate was set at 0.8 mL /min. The column temperature was maintained at 30 oC. The LC eluate was detected by an electrospray ionization(ESI) source operated in the positive ion mode, and quantification was conducted using MRM of the transitions m/z 399.24→283.01 and m/z 415.19→178.00 for sunitinib and internal standard(IS, diltiazem hydrochloride), respectively. The calibration curve was linear in the range of 2–600 ng/m L. The lower limit of quantification was 2 ng/mL. The method also exhibited satisfactory results in terms of sensitivity, specificity, accuracy(with relative error ranging from –4.0% to 1.1%), precision(with intra- and inter-day relative standard deviations ranging from 2.8% to 9.5%), matrix effect, recovery as well as stability. Taken together, our newly developed method was reliable to monitor sunitinib concentrations in rabbit plasma.
基金the Deanship of Scientific Research at King Saud University for funding this research group,No. RG-1435-041
文摘OBJECTIVE:To investigate the effect of black catechu(BC) on the pharmacokinetics of theophylline(CYP1A2 substrate,with narrow therapeutic index)in rabbits.METHODS:In the present investigation the effect of BC on the pharmacokinetics of theophylline,a CYP1A2 substrate was determined.In the study,BC(264 mg/kg,p.o.) or saline(control group) was given to rabbits for 7 consecutive days and on the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration,time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%,35.71%and 15.03%,respectively.While decreases in clearance,volume of distribution,and half-life were observed.It is suggested that BC pretreatment decreases the CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.