Pharmacokinetics of oral cefatrizine in pregnant and non-pregnant women with reference to fetal distribution.
OBJECTIVE
To investigate the effect of gestation on the pharmacokinetics of orally administered beta-lactams, choosing cefatrizine as the model antibiotic.


METHODS
A tertiary teaching hospital.


METHODS
Prospective study.


METHODS
In 20 women with affected fetuses, 17 by beta-thalassemia major and 3 with congenital malformations, termination of gestation between 19 and 24 weeks was induced by intra-amniotic administration of prostaglandin F(2)(alpha). Pharmacokinetics of cefatrizine in maternal and fetal blood were studied after the administration of three 1 g doses of oral cefatrizine, every 12 h. Twenty female non-pregnant volunteers consisted the control group.


RESULTS
Gestation was found to decrease substantially both cefatrizine oral bioavailability and maximum serum plasma concentration (42.8 and 44.5%, respectively) but increased elimination half-life. This effect can be attributed to a substantial increase of the apparent volume of distribution of cefatrizine in relation to a moderate increase of clearance that occurs during pregnancy. Fetal serum cefatrizine levels were lower for the first few hours after administration and then exceeded the corresponding maternal ones.


CONCLUSIONS
Our results indicate that gestation decreases the oral bioavailability of cefatrizine. A delay in the maternal drug elimination compared to non-pregnant controls was more pronounced in the fetus.
Papantoniou
N
N
First Department of Obstetrics and Gynecology, University of Athens, Alexandra Hospital, Athens, Greece.
Ismailos
G
G
Daskalakis
G
G
Karabinas
C
C
Mesogitis
S
S
Papapanagiotou
A
A
Antsaklis
A
A
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002436:Cefatrizine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006115:Greece; D006207:Half-Life; D006784:Hospitals, Teaching; D006801:Humans; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D011247:Pregnancy / Q000378:metabolism*; D011446:Prospective Studies; D012016:Reference Values; D013997:Time Factors
D000900:Anti-Bacterial Agents; D002436:Cefatrizine