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It has been shown previously that cefoxitin was not detectable in the milk following an intramuscular injection of 1 Gm to mothers. In the present study, using a more sensitive HPLC method, we have shown in five women that low concentrations of cefoxitin (0.25 to 0.65 micrograms/ml) are measured in the milk after the intramuscular injection of 2 Gm.

Cefoxitin is a new semisynthetic cephamycin derivative with broad bactericidal activities. In order to determine the extent of the transplacental transfer of cefoxitin, 35 pregnant women received 1 Gm cefoxitin intramuscularly 15 to 180 minutes before normal or Caesarean delivery. Cefoxitin was measured microbiologically in maternal blood (multiple-time samples), umbilical blood (one-time sample), and amniotic fluid in the cases of Caesarean sections. The mammary excretion of cefoxitin injected at the same dose was investigated by measuring cefoxitin in the milk of 16 nursing mothers. In the maternal blood, a peak plasma level of approximately 25 microgram/ml was reached 30 minutes after the 1-Gm intramuscular injection. A clear-cut passage of cefoxitin in the umbilical cord blood was demonstrated. In the fetal blood, a peak level of 15 microgram/ml was obtained 45 minutes after the injection. No cefoxitin was detectable in any of the milk samples from 30 minutes to 24 hours after the 1-Gm intramuscular injection.

The pharmacokinetics of Cefoxitin were studied in rabbits with normal renal function and with varying degrees of renal impairment induced experimentally by uranyl nitrate. All animals received a single intramuscular (i.m.) dose of 40 mg kg-1 of the antibiotic. The concentrations of Cefoxitin were determined in plasma, urine, and bile by a microbiologic plate diffusion method. The antibiotic follows a two-compartment open kinetic model. In rabbits with renal impairment there is a decrease in alpha, beta, K12, K21, Ka and an increase in Vd and the (AUC)infinity zero with respect to the values obtained for rabbits with normal renal function. Linear relationships are established between log beta and log K13 and the serum creatinine. Biliary excretion of Cefoxitin is increased in states of renal impairment. A linear relationship is established between the percentage of the dose excreted in the bile and the serum creatinine.

Multicompartmental pharmacokinetics involves the four volumes: Vc = volume of the central compartment; Vss = volume of distribution steady-state; V beta = volume of distribution beta; and Vext = the extrapolated volume of distribution. The ratio Vc/Vext is indicative of the degree of multicompartmental character of a set of data. The quantity (Vext/V beta)--1 is the fractional error in the total clearance when one assumes a monoexponential rather than a polyexponential equation for disposition of a drug. The ratio Vss/V beta indicates how well the one-compartment body model predicts average amounts of drug in the body when a multicompartmental model is actually operative. The quantity (Vss/Vc)--1 is equal to either k12/k21 or k12/k21 + k13/k31 of the two- and three-compartmental mammillary models. Examples from the literature are reported and discussed.