Ceftriaxone distribution and protein binding between maternal blood and milk postpartum

OBJECTIVE: To study postpartum distribution and protein binding of ceftriaxone (CTX) between maternal blood and milk and to discuss risk factors and possible impact for the neonate. DATA SOURCES: Reference articles and books are identified in the text. DATA SYNTHESIS: CTX distribution and protein binding between maternal blood and milk postpartum were studied in a patient at term presenting with acute pyelonephritis caused by Escherichia coli. The antibiotic therapy prescribed pending bacteriology results consisted of CTX 2 g/d, ornidazole 1 g/d, and tobramycin 3 mg/kg/d. Pharmacokinetics of total CTX were studied after the first 2-g infusion. At plateau (i.e., two days after delivery; seventh infusion), pharmacokinetics and milk distribution of total and free CTX also were studied. No accumulation of CTX was noted in the plasma at plateau. When high dosages of CTX are used (approximately 2 g), its penetration into the milk is important (i.e., protein binding capacity is overwhelmed). No notable adverse reactions occurred in mother or child. Thus, an important diffusion into the milk (4.4 percent of the dose) appears not to be clinically important. Our knowledge of both metabolism and milk distribution of drugs with high protein binding (> or = 95 percent) and an acid characteristic should be expanded to better understand their use during both the pregnancy and postpartum periods. Finally, the child of the patient described here has normal initial growth and development at the present time. CONCLUSIONS: Caution should be taken when drugs such as CTX, which have both high protein binding (> or = 95 percent) and an acid characteristic are administered to breastfeeding women. Drugs of this type should be systematically investigated to better understand their use during pregnancy and postpartum.

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