Dudley M N
Antiinfective Pharmacology Research Unit, University of Rhode Island College of Pharmacy, Roger Williams Medical Center, Providence 02908, USA.
Am J Health Syst Pharm. 1995 Mar 15;52(6 Suppl 2):S23-8. doi: 10.1093/ajhp/52.6_Suppl_2.S23.
Pharmacokinetic and pharmacodynamic considerations in in vitro susceptibility testing are described, and the integration of pharmacokinetic and pharmacodynamic concepts in dosage-regimen design is explored. Both the amount of beta-lactamase produced per unit of time and the amount of beta-lactamase inhibitor supplied greatly influence susceptibility to beta-lactam antibiotics. The goal should be to supply enough beta-lactamase to render the bacteria functionally beta-lactamase negative. In susceptibility testing, the amount of inhibitor may be more important than the ratio between the beta-lactam antibiotic and the inhibitor. Irreversible inactivation of beta-lactamases by inhibitors allows for a period of killing of bacteria by beta-lactams, even when concentrations of the inhibitor fall to concentrations below those tested in vitro. The integration of pharmacokinetic and pharmacodynamic concepts allows for comparisons between in vitro and in vivo drug exposure. With some antibiotic-inhibitor combinations, it may be possible to extend the dosage interval if an adequate amount of inhibitor is provided over the course of therapy.
本文描述了体外药敏试验中的药代动力学和药效学考量，并探讨了药代动力学和药效学概念在给药方案设计中的整合。每单位时间产生的β-内酰胺酶量以及所提供的β-内酰胺酶抑制剂的量，都对β-内酰胺类抗生素的敏感性有很大影响。目标应该是提供足够的β-内酰胺酶，使细菌在功能上表现为β-内酰胺酶阴性。在药敏试验中，抑制剂的量可能比β-内酰胺类抗生素与抑制剂之间的比例更为重要。抑制剂对β-内酰胺酶的不可逆失活作用，使得β-内酰胺类药物能够在一段时间内杀灭细菌，即使抑制剂浓度降至低于体外试验所测浓度。药代动力学和药效学概念的整合，使得体外和体内药物暴露情况得以比较。对于某些抗生素-抑制剂组合，如果在治疗过程中提供足够量的抑制剂，有可能延长给药间隔。
