Variations in Amoxicillin Pharmacokinetic/Pharmacodynamic Parameters May Explain Treatment Failures in Acute Otitis Media
Variations in Amoxicillin Pharmacokinetic/Pharmacodynamic Parameters May Explain Treatment Failures in Acute Otitis Media
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阿莫西林药代动力学/药效学参数的变化可能解释急性中耳炎的治疗失败
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
M. Reed
中科院分区：
文献类型：
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作者：
M. Pichichero;M. Reed
药代动力学/药效学（PK/PD）模型和Monte Carlo模拟表明，阿莫西林作为肺炎链球菌和流感嗜血杆菌急性中耳炎（AOM）感染的治疗很少失败，除非S. pneumoniae是高度青霉素耐药的，或者H.流感病毒产生β-内酰胺酶。然而，已经描述了这种期望的重要且并非罕见的例外情况。本综述的目的是确定治疗儿童AOM的阿莫西林PK/PD参数的生物学变化，并评估这些变化是否可以解释为什么常用的阿莫西林PK/PD模型在预测该临床环境中每例患者的结局时不完美。为此，对MEDLINE（1966-2006）和EMBASE（1974-2006）进行了文献检索，以识别评价氨苄西林或阿莫西林肠道吸收、血清浓度和/或中耳液（MEF）浓度的研究。对确定用于审查的研究的分析表明，阿莫西林的肠道生物利用度取决于被动扩散和可饱和的“泵”机制，该机制产生抗菌剂的可变血清浓度。实际上，口服给药后，阿莫西林的血清（5- 30倍）和MEF（高达20倍）浓度在患者之间存在显著差异，15-35%的儿童MEF中未检测到阿莫西林。这些结果表明，PK/PD参数的变异性可能影响血清和MEF中的阿莫西林浓度，可能解释了一些AOM治疗失败。
Pharmacokinetic/pharmacodynamic (PK/PD) modeling and Monte Carlo simulations suggest that amoxicillin should rarely fail as therapy for Streptococcus pneumoniae and Haemophilus influenzae acute otitis media (AOM) infections except when the S. pneumoniae are highly penicillin resistant or the H. influenzae are β-lactamase producing. However, important and not infrequent exceptions to this expectation have been described. The objective of this review was to define the biologic variations in amoxicillin PK/PD parameters for the treatment of AOM in children and assess whether these variations could explain why the commonly employed amoxicillin PK/PD model is imperfect in predicting outcome for every patient in this clinical setting. To this end, a literature search of MEDLINE (1966–2006) and EMBASE (1974–2006) was conducted to identify studies that evaluated ampicillin or amoxicillin intestinal absorption, serum concentrations, and/or middle ear fluid (MEF) concentrations. Analysis of studies identified for review showed that the intestinal bioavailability of amoxicillin depends on passive diffusion and a saturable ‘pump’ mechanism that produces variable serum concentrations of the antibacterial agent. Indeed, substantial differences from patient to patient in serum (5- to 30-fold) and MEF (up to 20-fold) concentrations of amoxicillin occur following oral administration, and 15–35% of children have no detectable amoxicillin in MEF. These findings suggest that variability in PK/PD parameters may impact amoxicillin concentrations in serum and MEF, possibly explaining some AOM treatment failures.