Comparison of the Pharmacokinetics of Cephradine and Cefazolin in Pregnant and Non-Pregnant Women

Abstract

The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy. For both drugs most pharmacokinetic parameters were altered in pregnancy. The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin). Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin). Consequently, total body clearance was increased during pregnancy. A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine. The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy. It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

“…This is consistent with the common trend used for cefazolin PK analysis found in the literature (10). In our study, the volume of distribution and clearance values for cefazolin (Table 2) were in good agreement with the values reported in the literature for nonpregnant and pregnant adults (9,(28)(29)(30)(31)(32).…”

“…Therefore, pregnancy may be associated with increased drug dilution. However, consistent with the findings of Philipson et al (30), we were unable to establish pregnancy-related changes in the volume of distribution.…”

“…Popovic et al failed to demonstrate a significant difference in cefazolin disposition between women undergoing cesarean delivery at term compared with women undergoing gynecological surgery (12). In contrast, Philipson et al reported a 57% increase in cefazolin antepartum clearance compared with postpartum values (30). Our result (Table 2) supports the finding of Philipson et al (30), where clearance estimate during pregnancy (7.2 liters/h) is almost two times greater than that following delivery (4.1 liters/h).…”

Role of the Constitutive Androstane Receptor in Xenobiotic-Induced Thyroid Hormone Metabolism

“…An alternative explanation is that higher estrogen and progesterone levels during pregnancy may activate CAR or its closest relative, pregnane X receptor, and increase TH metabolism (85,86). Consistent with this, serum levels of anticonvulsants as well as other drugs decrease during pregnancy by as much as 40%, apparently due to an increase their hepatic metabolism (77,(87)(88)(89)(90). It is believed that this is a consequence of the higher estrogen levels in pregnant women because similar effects have been reported for nonpregnant women on oral estrogen contraceptives (91,92).…”

The Impacts of the Physiological Changes Occurring During Pregnancy on Pharmacokinetic Mechanisms

“…Bu durum, kararlı ilaç konsantrasyonunu düşürebilmekle birlikte, sadece çok nadir durumlarda doz artışı gerektirmektedir (21)(22)(23)(24)(25). Örneğin, enoksaparin gibi ilaçların klerensinin artması, gebelik sırasında trombozis oluşu-munu engellemek için dozun artırılmasını gerektirebilmektedir (26).…”