This is a prospective, non-randomized, phase I study design evaluating the in vivo activities and expression of OCT1 and BCRP in mammary gland of lactating women at three time points postpartum.
Each woman will receive a single oral dose of cimetidine 200 mg on each of 3 study days (3-5 weeks, 3-4 months, and 6-8 months postpartum) followed by serial collection of blood, urine and breast milk samples over 12-hours. Cimetidine concentrations will be assay using a validated LC/MS/MS assay. Subjects will be genotyped for OCT1 and BCRP. Mammary epithelial cells will be isolated from breast milk and transporter expression will be quantified. Each woman will serve as her own control.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
50
Cimetidine will serve as the probe drug
University of Washington
Seattle, Washington, United States
RECRUITINGMammary clearance of cimetidine
Cimetidine excretion into breast milk at three postpartum stages
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Mammary epithelial cell expression of BCRP
BCRP protein expression in MECs at three postpartum stages
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Mammary epithelial cell expression of OCT1
OCT1 protein expression in MECs at three postpartum stages
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Cimetidine relative infant dose and infant concentration
cimetidine relative infant dose (RID) and infant concentration
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Relationship between OCT1 expression and activity
Effect of time postpartum on OCT1 protein expression in MECs and correlation with cimetidine mammary CL
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine CL/F
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine renal CL
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
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Effects of time postpartum on cimetidine renal secretion CL
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine mammary CL
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine AUC
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine Cmax
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine Tmax
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine half-life
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine apparent oral volume of distribution
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Maternal cimetidine PK
Effects of time postpartum on cimetidine elimination rate constant
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum
Relationship between BCRP expression and activity
Effect of time postpartum on BCRP protein expression in MECs and correlation with cimetidine mammary CL
Time frame: 3-5 weeks, 3-4 months and 6-8 months postpartum