TY - JOUR
T1 - Active transport of cimetidine into human milk
AU - Oo, Cheah Y.
AU - Kuhn, Robert J.
AU - Desai, Nirmala
AU - McNamara, Patrick J.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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U2 - 10.1016/0009-9236(95)90175-2
DO - 10.1016/0009-9236(95)90175-2
M3 - Article
C2 - 7586949
AN - SCOPUS:0028785929
SN - 0009-9236
VL - 58
SP - 548
EP - 555
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 5
ER -