Kurihara A, Hisaoka M, Mikuni N, Kamoshida K
Product Development Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
J Pharmacobiodyn. 1992 Jul;15(7):325-32. doi: 10.1248/bpb1978.15.325.
The neurotoxic potential of panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, was compared with that of imipenem/cilastatin (IPM/CS). The drug concentration in cerebrospinal fluid (CSF) at the onset of epileptogenic electroencephalographic (EEG)-activity and the drug distribution into the central nervous system (CNS) were evaluated. Epileptogenic reactions correlated well with drug levels in CSF, but not with drug levels in circulating plasma. The concentration of PAPM in CSF at the onset of epileptogenic EEG-activity was almost twice that of IPM, suggesting that neurotoxic activity of PAPM is about half that of IPM. In addition, in terms of incidence percent for the epileptogenic EEG-activity, PAPM/BP was found to be less toxic than IPM/CS within the dose of 1.0-1.2 g/kg. Concentrations of PAPM in CSF and brain extracellular fluid after PAPM/BP i.v. infusion were comparable with those of IPM after IPM/CS infusion, indicating the similar characteristics of distribution into the CNS for the two antibiotics. From these results of pharmacologic effects and drug distributions, it is suggested that the neurotoxicity of PAPM/BP is less than half that of IPM/CS.
将新型碳青霉烯类抗生素帕尼培南/倍他米隆（PAPM/BP）的神经毒性潜力与亚胺培南/西司他丁（IPM/CS）进行了比较。评估了致痫性脑电图（EEG）活动开始时脑脊液（CSF）中的药物浓度以及药物在中枢神经系统（CNS）中的分布情况。致痫反应与脑脊液中的药物水平密切相关，但与循环血浆中的药物水平无关。致痫性EEG活动开始时脑脊液中PAPM的浓度几乎是IPM的两倍，这表明PAPM的神经毒性活性约为IPM的一半。此外，就致痫性EEG活动的发生率而言，发现在1.0 - 1.2 g/kg剂量范围内，PAPM/BP的毒性低于IPM/CS。静脉输注PAPM/BP后，脑脊液和脑细胞外液中PAPM的浓度与输注IPM/CS后IPM的浓度相当，表明这两种抗生素在CNS中的分布特征相似。从这些药理作用和药物分布结果来看，提示PAPM/BP的神经毒性小于IPM/CS的一半。
