[Determination of the ratio of serum concentrations of tobramycin between fetus and mother at birth. A model of small scale pharmacokinetics].
Thirty women at term presenting with fever greater than or equal to 38 degrees C during labour were given a synergic combination of tobramycin-amoxicillin. Gestational ages ranged from 37 6/7 to 41 2/7 weeks. A single dose of 3 mg/kg of tobramycin was given every day intravenously. Feto-maternal tobramycin concentrations (F/M ratios) were systematically determined at birth and allowed to make a small scale pharmacokinetic study. Two curves were plotted from the pharmacokinetic analysis of maternal and fetal measurements, showing an intravenous and an intramuscular profile respectively. A high positive linear correlation (R = 0.82) was found between the F/M ratios and the time (delta T, -hours-) measured from the last administration to the mother to the time of delivery. Elimination of the aminoglycoside was slowed down in newborns (t1/2 lambda z = 5.1 hours). In newborns tobramycin levels were always less than or equal to 6 mg/l and still greater than or equal to 1 mg/l 6 hours after the last maternal injections. Measurement of F/M ratios allowed to study and compare the fetal and maternal pharmacokinetics facilitating (when necessary) the initial posologic adjustment in newborns. Such small scale pharmacokinetics could be extended, for a given gestational age, to other drugs with narrow therapeutic ranges. However, the size and the homogeneity of the population seem to be most important.
Bourget
P
P
Service de Pharmacie Clinique, Hôpital Antoine-Béclère, Clamart.
Fernandez
H
H
Demirdjian
S
S
Delouis
C
C
Frydman
R
R
D000658:Amoxicillin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001724:Birth Weight; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D014031:Tobramycin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000658:Amoxicillin; D014031:Tobramycin
Détermination des rapports de concentrations sériques foeto-maternelles de la tobramycine à la naissance. Un modèle de pharmacocinétique réduite.