共 21 条
SIMULATION OF AMOXICILLIN PHARMACOKINETICS IN HUMANS FOR THE PREVENTION OF STREPTOCOCCAL ENDOCARDITIS IN RATS
被引:26
作者:
FLUCKIGER, U
MOREILLON, P
BLASER, J
BICKLE, M
GLAUSER, MP
FRANCIOLI, P
机构:
[1] CHU VAUDOIS,DEPT INTERNAL MED,DIV INFECT DIS,CH-1011 LAUSANNE,SWITZERLAND
[2] UNIV ZURICH HOSP,DEPT MED,CH-8091 ZURICH,SWITZERLAND
关键词:
D O I:
10.1128/AAC.38.12.2846
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
The pharmacokinetic determinants of successful antibiotic prophylaxis of endocarditis are not precisely known. Differences in half-lives of antibiotics between animals and humans preclude extrapolation of animal results to human situations. To overcome this limitation, we have mimicked in rats the amoxicillin kinetics in humans following a 3-g oral dose (as often used for prophylaxis of endocarditis) by delivering the drug through a computerized pump. Rats with catheter-induced vegetations were challenged with either of two strains of antibiotic-tolerant viridans group streptococci. Antibiotics were given either through the pump (to simulate the whole kinetic profile during prophylaxis in humans) or as an intravenous bolus which imitated only the peak level of amoxicillin (18 mg/liter) in human serum. Prophylaxis by intravenous bolus was inoculum dependent and afforded a limited protection only in rats challenged with the minimum inoculum size infecting greater than or equal to 90% of untreated controls. In contrast, simulation of kinetics in humans significantly protected animals challenged with 10 to 100 times the inoculum of either of the test organisms infecting greater than or equal to 90% of untreated controls. Thus, simulation of the profiles of amoxicillin prophylaxis in human serum was more efficacious than mere imitation of the transient peak level in rats. This confirms previous studies suggesting that the duration for which the serum amoxicillin level remained detectable (not only the magnitude of the peak) was an important parameter in successful prophylaxis of endocarditis. The results also suggest that single-dose prophylaxis with 3 g of amoxicillin in humans might be more effective than predicted by conventional animal models in which only peak levels of antibiotic in human serum were simulated.
引用
收藏
页码:2846 / 2849
页数:4
相关论文