Bourget P, Fernandez H, Delouis C, Taburet A M
Laboratory of Pharmacology and Toxicology, Hôpital Antoine Beclere, Clamart, France.
J Clin Pharm Ther. 1991 Jun;16(3):167-76. doi: 10.1111/j.1365-2710.1991.tb00300.x.
The pharmacokinetics of tobramycin, an aminoglycoside antibiotic, was investigated after a short intravenous infusion and once-daily dose regimen in two groups of nine pregnant women during the second (Group 1) and the third (Group 2) trimester of pregnancy. During these periods, the risk of infectious diseases is increased. Plasma concentrations of tobramycin were measured by fluorescence polarization immunoassay. The decrease in clearance (21%), at 28 weeks and more of gestation leads to an increase in half-life and the mean residence time (MRT) in the second group (33 and 29% respectively). The volume of distribution was unchanged in the two groups. No accumulation of the drug was observed in pregnant women. Pharmacokinetic disorders are correlated with the term and moreover with the weight deviation of women, i.e. the growth of the fetus. These findings suggest accumulation of the aminoglycoside antibiotic in the fetus. Moreover, the efficacy and the safety of this therapeutic regimen were excellent. To limit the potential nephrotoxicity and ototoxicity of tobramycin for the mother and the fetus, a once-daily dose regimen seems to be acceptable for the treatment of non-neutropenic pregnant women.
在两组各9名处于妊娠中期（第1组）和晚期（第2组）的孕妇中，研究了氨基糖苷类抗生素妥布霉素在短期静脉输注和每日一次给药方案后的药代动力学。在这些时期，传染病风险增加。通过荧光偏振免疫测定法测量妥布霉素的血浆浓度。在妊娠28周及以上时，清除率下降（21%），导致第2组的半衰期和平均驻留时间（MRT）增加（分别增加33%和29%）。两组的分布容积均无变化。在孕妇中未观察到药物蓄积。药代动力学紊乱与孕周相关，而且与孕妇体重偏差（即胎儿生长）相关。这些发现提示氨基糖苷类抗生素在胎儿体内蓄积。此外，该治疗方案的疗效和安全性良好。为限制妥布霉素对母亲和胎儿的潜在肾毒性和耳毒性，每日一次给药方案对于非中性粒细胞减少的孕妇治疗似乎是可接受的。
