| Objective: Selecting gentamicin as an example of aminoglycoside antibiotics, it is to study the effects of different administration time on kidney toxicity, serum concentrations, and pharmacokinetic parameters in rats.Method: 1. The HPLC-UV assay of gentamicin was developed after precolumn derivatization. In this method, FDNB was used as derivatizer, and vertilmicin was used as internal standard. The serum concentrations of gentamicin in rats were examined by developed HPLC-UV method. 2. The rats was divided into 6 groups: control group; single daily dose group(N100 and D100 group was intramuscularly administrated 100mg/kg gentamicin at 1:00 and 13:00 respectively); the mutiple dose groups(N90+D10 group, N70+D30 group, N50+D50 group, 100mg/kg/d gentamicin was adminstrated in twice at 1:00 and 13:00). Different dose for these groups was respectively 90mg/kg+10mg/kg, 70mg/kg+30mg/kg and 50mg/kg+50mg/kg. Gentamicin was administrated intramuscularly. The difference of weight, urine protein, BUN and Cr level was observed at the 1st, the 10th and the 20th day after administrations. 3. The serum concentrations of gentamicin at 0.25h, 0.5h, 1h, 2h, 5h, 8h was determined. This process was repeated at the 10th day and 20th day. C-T curves were depicted to caculate the pharmacokinetic parameters.Results: 1. Nephrotoxicity: At the 20th day after administration, Cr(115.82 ±23.85μmol/l) and BUN(11.34± 1.22mmol/l) of N50+D50 group was the highest. There were significant difference between these data and that ofthe 1st day after administration and of control group at the same time(P<0.05). The Cr(69.04 ± 4.75umol/l) and BUN(7.10 ± l.Olmmol/1) were the lowest among all groups. At the 20th day after administration, the N50+D50 group exhibited the lowest increase(P<0.05) in weight(194.69±30.68g), while the increase in weight(223.75±15.44g) of NlOO group was close to that of control group.2. Gentamicin Concentrations: The peak concentration of single dose daily group(N100 group and DlOO group) was respectively 527.72 + 93.19ug/ml and 806.44 + 28.95ng/ml at the 10th day after administration(P<0.05). Among the mutiple administration regimens, the peak concentration of N50+D50 group at 20th day after administration was 606.57+144.11 jig/ml, which was higher than that of groups of different doses(592.17 + 82.77ug/ml and 514.67+ 15.67|^g/ml), but there was no significantly statistical difference.3. The pharmacokinetic parameters: At the 20th day after administration, AUC(o-inn (1195.84±309.42ng/ml/h) of N50+D50 group was the highest, and that(621.71 +122.5lug/ml/h) of NlOO group was the lowest(P<0.05) among these groups. The CLs of N50+D50 group(0.0784 + 0.0183L/kg/h) was the smallest, while that of NlOO group(0.1484 + 0.0280L/kg/h) was largest. At the 1st, the 10th and the 20th day after administration, T\a of the NlOO group was the shortest(respectively 1.03 + 0.05h, 1.32 + 0.08h and 1.24 + 0.18h) while that of N50+D50 group was the longest(respectively 2.04 + 0.28h, 1.90 + 0.01h and 2.11 ±0.5 lh(P<0.05).Conclusion: In chronological dosage regimens, the nephrotoxicity is lowest when dosing at active phase for single daily dose. The range of concentrations was narrow when dosing at active phase than that of dosing at...
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