Pharmacokinetics of Oral Cefatrizine in Pregnant and Non-Pregnant Women with Reference to Fetal Distribution

Abstract

Objective: To investigate the effect of gestation on the pharmacokinetics of orally administered β-lactams, choosing cefatrizine as the model antibiotic. Setting: A tertiary teaching hospital. Design: Prospective study. Methods: In 20 women with affected fetuses, 17 by β-thalassemia major and 3 with congenital malformations, termination of gestation between 19 and 24 weeks was induced by intra-amniotic administration of prostaglandin F₂_α. 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.

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

“…The scope of studies to investigate both PK and clinical outcome data seems to be dependent on drug class. For example, none of the studies that investigated antibiotics [47,52,53] or anesthetic and analgesic drugs [102] provided data on clinical outcomes. On the other hand, studies of addiction management drugs and antidepressant drugs reported clinical data, showing a positive correlation between decreased drug exposure and diminished clinical effects in pregnancy [70,202].…”

Clinical Therapeutics in Pregnancy

“…For example, cefatrizine, a cephalosporin antibiotic, is eliminated by renal mechanisms and not metabolized. Pregnancy reduces the antibiotic's oral availability by 43%, serum concentration by 45%, and extends its elimination half-life by one hour [7]. …”

Pharmacokinetic Behaviors of Orally Administered Drugs

“…A substantial decrease was observed in AUC 0−12h and C max (43 and 44%, respectively) in pregnant women compared to that in nonpregnant women. Furthermore, a 1.63-fold (2.48 vs 1.52 h) increase was observed in the half-life of the drug in pregnant women (Papantoniou et al, 2007).…”

“…42 Cefatrizine serum concentrations (mean ± SD, μg/mL) in 20 female volunteers (circles) and 20 women in the 23rd week of gestation (squares) after the administration of the third oral dose of 1 g cefatrizine every 12 h. Source: Reproduced fromPapantoniou et al (2007) with permission.…”