Influence of Pregnancy on Ceftriaxone, Cefazolin and Gentamicin Pharmacokinetics in Caesarean Vs. Non-pregnant Sectioned Women

Objective: To study the effect of pregnancy on postoperative ceftriaxone, cefazolin and gentamicin elimination rate constant, half-life, volume of distribution and systemic clearance.

Methods: Fifty-four patients undergoing caesarean section and 12 undergoing gynaecological surgery were given intravenous dose of ceftriaxone, cefazolin or gentamicin immediately before the operation, for chemoprophylaxis. The levels of antibiotics were measured in blood plasma, amniotic fluid and umbilical cord blood plasma by HPLC for the cephalosporins and by fluorescence polarization immunoassay for gentamicin. Pharmacokinetic parameters were estimated using a one-compartment model.

Results: Pregnancy significantly influenced the pharmacokinetics of ceftriaxone and gentamicin, but not that of cefazolin. Ceftriaxone constant of elimination decreased statistically significantly in caesarean-sectioned women relative to the non-pregnant subjects. Gentamicin constant of elimination increased significantly in caesarean-sectioned women relative to the controls. The concentrations of antibiotics in umbilical cord blood were higher, whereas they were substantially lower in amniotic fluid than in maternal plasma. Six hours after antibiotic administration, only the cefazolin concentrations exceeded the MIC for sensitive bacteria both in pregnant and in non-pregnant patients.

Conclusion: Analysis of the pharmacokinetic data suggests that a single-dose of cefazolin may well be the optimal preoperative prophylactic treatment for obstetrical and gynaecological surgical procedures.