[Clinical pharmacokinetics of ceftriaxone during the third trimester of pregnancy and study of its transplacental passage in two patients].
The purpose of this study was to determine ceftriaxone (CTX) pharmacokinetics during pregnancy. Six women (26 to 34 years of age) admitted for chorioamnionitis (n = 4) or pyelonephritis (n = 2) were included. Gestational age ranged from 29 1/7 to 40 5/7 weeks. Initial intravenous treatment was ceftriaxone (CTX) (2 g/d), tobramycin (3 mg/kd/d) and ornidazole (1 g/d). Blood specimens were collected during the first treatment day (D1) to determine the primary pharmacokinetic profile of CTX then at steady-state (D7) to look for systemic accumulation. In two patients, transplacental passage of CTX was evaluated by determining the ratio of fetal and maternal concentrations (F/M) at delivery. Plasma CTX levels were determined using high-performance liquid chromatography. A noncompartmental method was used for pharmacokinetic analysis. Each patient served as her own control. Data obtained on D1 and D7 were compared using Wilcoxon's test (values of p < or = 0.05 were considered significant). A group of healthy controls given a similar regimen was also used. 1) Tolerance was outstanding, recovery was achieved in every case, and there were no premature deliveries. 2) No evidence of accumulation of CTX was found and kinetic profiles on D1 and D7 were not significantly different. 3) Mean kinetic parameter values were closely similar to those found in healthy volunteers. 4) Residual levels of total CTX and free CTX determined after 24 hours were greater than the minimal inhibitory concentration (MICs) of susceptible organisms. 5) The usual recommended dosage of CTX (2 g/d) proved adequate during the third trimester of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Bourget
P
P
Service de Pharmacie Clinique, Hôpital Antoine Béclère, Clamart, France.
Quinquis
V
V
Fernandez
H
H
Frydman
R
R
D000328:Adult; D002443:Ceftriaxone / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002821:Chorioamnionitis / Q000188:drug therapy / Q000382:microbiology; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011263:Pregnancy Trimester, Third; D011512:Proteus Infections / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*
D002443:Ceftriaxone
Pharmacocinétique clinique de la ceftriaxone au cours du troisième de la grossesse et étude de son passage transplacentaire dans deux cas.