Pharmacokinetics of tobramycin in pregnant women. Safety and efficacy of a once-daily dose regimen.
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.
Bourget
P
P
Laboratory of Pharmacology and Toxicology, Hôpital Antoine Beclere, Clamart, France.
Fernandez
H
H
Delouis
C
C
Taburet
A M
AM
D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D012044:Regression Analysis; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D014031:Tobramycin