Fujishita O, Nakashima K, Hirakawa M, Otsubo K, Higuchi S, Aoyama T
Department of Hospital Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
Chem Pharm Bull (Tokyo). 1990 Sep;38(9):2518-22. doi: 10.1248/cpb.38.2518.
The correlative equations between the molecular volume and the qualitative indication (hR) for beta-lactam antibiotics, the reaction products between beta-lactam antibiotics and kanamycin, and the degradation products of beta-lactam antibiotics were hR = 0.32 + 0.080 VA2/3//Z/(N = 15, r = 0.972 for penicillins) and hR = 0.04 + 0.072 VA2/3//Z/(N = 12, r = 0.987 for cephems). Where VA is van der Waals volume (A3/molecule), hR is the relative step height in the isotachopherogram, and Z is the electric change, respectively. According to these equations, the molecular volumes of the reaction products between beta-lactam antibiotics and the other aminoglycoside antibiotics, and those of the degradation products of beta-lactam antibiotics can be estimated from the value of hR. Also according to the step height in the isotachopherogram, the reaction products or the degradation products may be estimated directly when the electric charge is known. It was confirmed that a molecule of aminoglycoside antibiotics reacted with a molecule of beta-lactam antibiotics. Therefore, the inactivation of aminoglycoside antibiotics is much greater than for beta-lactam antibiotics when the clinical doses of these antibiotic combinations are used.
β-内酰胺类抗生素的分子体积与定性指标(hR)、β-内酰胺类抗生素与卡那霉素的反应产物以及β-内酰胺类抗生素的降解产物之间的相关方程分别为:hR = 0.32 + 0.080 VA2/3//Z/(N = 15,青霉素类的r = 0.972)和hR = 0.04 + 0.072 VA2/3//Z/(N = 12,头孢菌素类的r = 0.987)。其中,VA是范德华体积(A3/分子),hR是等速电泳图中的相对步高,Z分别是电荷。根据这些方程,可以从hR值估算β-内酰胺类抗生素与其他氨基糖苷类抗生素的反应产物以及β-内酰胺类抗生素降解产物的分子体积。同样,根据等速电泳图中的步高,当已知电荷时,可以直接估算反应产物或降解产物。已证实一分子氨基糖苷类抗生素与一分子β-内酰胺类抗生素发生反应。因此,当使用这些抗生素组合的临床剂量时,氨基糖苷类抗生素的失活程度远大于β-内酰胺类抗生素。