Active transport of cimetidine into human milk

Cheah Y. Oo, Robert J. Kuhn, Nirmala Desai, Patrick J. McNamara

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Most xenobiotics are transferred from blood into breast milk by passive diffusion. However, an active transport mechanism has been speculated for cimetidine, and the purpose of this study was to characterize cimetidine transfer into human milk. Twelve healthy lactating volunteers received single oral doses of 100, 600, and 1200 mg cimetidine in a randomized, crossover design on 3 different days. Blood and milk specimens were collected and assayed for cimetidine. In vitro measurements, including skim to whole milk concentration ratio, milk pH, and free fractions in serum and milk were used for a diffusion model prediction of milk to serum concentration ratio of cimetidine; the mean milk/serum ratio (± SD) was 1.05 ± 0.18. The observed milk/serum ratio (5.77 ± 1.24) was 5.5 times higher than the milk/serum ratio predicted by diffusion. The observed milk/serum ratio for the three dosing regimens were not significantly different from one another. Time of peak concentration (t(max)) in milk (3.3 ± 0.7 hours) displayed a delay compared with serum t(max) (1.7 ± 0.6 hours). Oral clearance for 1200 mg cimetidine dose (0.47 ± 0.11 L/hr/kg) was significantly lower compared with oral clearance values for 100 and 600 mg cimetidine doses (0.59 ± 0.11 and 0.57 ± 0.13 L/hr/kg, respectively). The maternal dose of cimetidine ingested by a suckling infant based on body weight was estimated to be 6.7%, which appears to be safe under normal conditions. This study provides the first definitive evidence of an active transport system for drug transfer into human milk, which may have broader consequences for the suckling infant.

Original languageEnglish
Pages (from-to)548-555
Number of pages8
JournalClinical Pharmacology and Therapeutics
Issue number5
StatePublished - 1995

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Active transport of cimetidine into human milk'. Together they form a unique fingerprint.

Cite this