The Pharmacokinetic Profiles of Pre-Operative Prophylactic Cefepime Application in Pregnant and Non-Pregnant Women Undergoing Surgical Interventions Using a Fully Validated Liquid Chromatographic Method

Abstract

Pregnancy alters pharmacokinetic profile of many drugs, because of altering body volume and metabolism rate. Therefore, dosage rates and concentrations of drugs must be controlled during pregnancy. Here, we identified the pharmacokinetic profile of pre-operatively given cefepime in caesarean section and gynecological operations using a simple, rapid, cost-effective and valid liquid chromatographic method. The chromatographic separation was performed using 40 mM, pH 3.2 phosphate buffer containing 6 % methanol as mobile phase at 0.30 mL min⁻¹ flow rate. Gradient elution with methanol was applied to get shorter analysis time without any interference from plasma endogens. During analyses, temperature of column, autosampler and detector were set as 30, 10 and 40 °C, respectively. The detection wavelength was 260 nm and ceftizoxime was used as internal standard. At the optimum conditions, the cefepime analysis from plasma samples was completed in 7 min. Cefepime was extracted from plasma samples using perchloric acid with a very high recovery rate (99.3 %). The method was fully validated according to the Food and Drug Administration guidelines for bioanalytical method validation, and found to be selective, linear, repeatable, reproducible and robust. After validation studies, the method was applied to five caesarean-sectioned and four non-pregnant sectioned women treated with pre-operative, prophylactic single intravenous dose of cefepime (1 g Maxipime^®) in order to determine pharmacokinetic profile of cefepime. Peak serum concentrations of cefepime in caesarean-sectioned women at the arterial port after infusion was 70.11 ± 10.74 μg mL⁻¹. The mean elimination half-life, volume of distribution and calculated area under the concentration–time curve (AUC)_0–∞ were 1.10 ± 0.23 h, 14.22 ± 2.29 L and 101.55 ± 10.99 μg h mL⁻¹ for caesarean-sectioned women; and 1.14 ± 0.21 h, 14.76 ± 2.92 L and 104.71 ± 36.34 μg h mL⁻¹ for non-pregnant sectioned women, respectively. The area under curve, elimination half-life, maximum plasma concentration and the mean distribution volume of cefepime were not changed in case of pregnancy.