Drug Excretion in Breast Milk

Lactation Clinical Trial

Official title:

Postpartum Activity and Expression of BCRP and OCT1 Drug Transporters in the Mammary Gland

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06056583
• Other study ID #: STUDY00018397
• Secondary ID: R01HD112282
• Status: Recruiting
• Phase: Phase 4
• Start date: December 4, 2023
• Est. completion date: September 30, 2028

Study information

• Verified date: May 2024
• Source: University of Washington
• Contact: Mary Hebert, PharmD, FCCP
• Phone: 206-616-5016
• Email: mhebert[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 30, 2028
• Est. primary completion date: September 30, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Study participants will include: healthy, lactating or pregnant and planning to breastfeed their infant, between 18-50 years of age, female and their nursing infant 3 weeks-8 months of age.

Exclusion Criteria:

• • Age <18 or > 50 years old.
• Smokers
• Following multiple gestation (twins, triplets etc.)
• Allergy to cimetidine
• Pregnancy
• Receiving medications that could lead to a drug interaction e.g.
• A: antacids, alprazolam, amphetamines, atazanavir, acalabrutinib, alosetron, amiodarone, amitriptyline, azelastine, amoxapine, alfuzosin,
• B: bisacodyl, bupropion, bosutinib,
• C: citalopram, chloroquine, codeine, clozapine, carmustine, clopidogrel, cyclosporine, carvedilol, cannabis, cefpodoxime, ceftibuten, clomipramine, cefditoren, chlordiazepoxide, chlorpromazine, cholecalciferol, cisapride, clonazepam, clorazepate, clomethiazole, carbamazepine,
• D: dofetilide, dihydrocodeine, duloxetine, delavirdine, dasatinib, domperidone, dothiepin, dilevalol, diltiazem, dutasteride, desipramine, doxepin, diazepam,
• E: escitalopram, epirubicin, eliglustat, estazolam, ethanol (on study day), ergocalciferol,
• F: fezolinetant, fluorouracil, finerenone, fexinidazole, flecainide, fluconazole, flurazepam, fosamprenavir, femoxetine,
• G: gefitinib, glipizide, glyburide, gliclazide, glimepiride,
• H: hydroxychloroquine, halazepam,
• I: infigratinib, imipramine, itraconazole,
• K: ketoconazole,
• L: ledipasvir, lornoxicam, labetalol, lidocaine, levoketoconazole, levomethadyl, lomitapide, loratadine,
• M: meperidine, morphine, mirtazapine, midazolam, metformin, metoclopramide, memantine, metronidazole, moclobemide,
• N: neratinib, nicotine, nebivolol, nisoldipine, nifedipine, nortriptyline, nimodipine, nicardipine, nilotinib, nitrazepam, nilvadipine, nitrendipine,
• O: oxycodone, octreotide, oxymorphone,
• P: posaconazole, piperaquine, pazopanib, pentoxifylline, paroxetine, phenytoin, pramipexole, propranolol, procainamide, phenindione, perfloxacin, praziquantel, protriptyline, prazepam, pontinib,
• Q: quinidine, quazepam, quinine,
• R: rilpivirine, roflumilast, risperidone, risedronate,
• S: succinylcholine, selpercatinib, sirolimus, secretin, sotorasib, sparsentan, sofobuvir, saquinavir, sertraline, sucralfate, sildenafil,
• T: terbinafine, tramadol, theophylline, tacrolimus, tizanidine, tolazoline, trimetrexate, tocainide, tamsulosin, timolol, tacrine, tolbutamide, trimipramine, tamoxifen, trimazosin, tinidazole, triazolam,
• V: vismodegib, verapamil, velpatasvir, venlafaxine, vardenafil,
• W: warfarin,
• Z: zalcitabine, zaleplon, zolmitriptan
• BCRP inhibitors: dasatinib, celecoxib, erlotinib, lopinavir, fostamatinib, docetaxel, barcitinib, imatinib, gefitnib, venetoclax, sunitinib, elacridar, Palbociclib, regorafenib, rucaparib, nilotinib, sorafenib, vemurafenib, afatinib, nelfinavir, paclitaxel, quercetin and alectinib
• BCRP inducers: venlafaxine, and dovitinib
• OCT inhibitors: trimethoprim, ranitidine, codeine, rocuronium, ganciclovir, acyclovir, dinoprostone, progesterone, prazosin, phenoxybenzamine, phenformin, procainamide, nicotine, choline, verapamil, quinine, pancuronium, disopyramide, desipramine, guanidine, probenecid, saquinavir, nelfinavir, chlorpheniramine, indinavir, reserpine, rucaparib, estradiol, pitolisant, choline, quinidine, amantadine, dexchlorpheniramine, doxazosin, efavirenz, nevirapine, clopidogrel, dacomitinib, gilteritinib, palbociclib, linagliptin, nintedanib, dronedarone, lasmiditan, formoterol, guanfacine, salmeterol, levofloxacin, osilodrostat, lurbinectedin, tirbanibulin cyproheptadine, infigratinib, atagepant, asciminib, abrocitinib, pacritinib, olaparib, tepotinib, tafenoquine, propranolol, oxprenolol, metoprolol, quinine, thiamine, norepinephrine, imipramine, grepafloxacine, amantadine, metformin, desipramine, famotidine, probenecid, cisplatin, quinacrine, amiloride, epinephrine, disopyramide, diphenhydramine, imatinib, flurazepam, bupropion, amiodarone, clopidogrel, cocaine, lamotrigine
• OCT inducers: none identified

Related Conditions & MeSH terms

• Lactation

Intervention

Drug:
• Cimetidine 200 MG
Cimetidine will serve as the probe drug

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mammary clearance of cimetidine	Cimetidine excretion into breast milk at three postpartum stages	3-5 weeks, 3-4 months and 6-8 months postpartum
Primary	Mammary epithelial cell expression of BCRP	BCRP protein expression in MECs at three postpartum stages	3-5 weeks, 3-4 months and 6-8 months postpartum
Primary	Mammary epithelial cell expression of OCT1	OCT1 protein expression in MECs at three postpartum stages	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Cimetidine relative infant dose and infant concentration	cimetidine relative infant dose (RID) and infant concentration	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Relationship between OCT1 expression and activity	Effect of time postpartum on OCT1 protein expression in MECs and correlation with cimetidine mammary CL	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine CL/F	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine renal CL	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine renal secretion CL	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine mammary CL	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine AUC	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine Cmax	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine Tmax	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine half-life	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine apparent oral volume of distribution	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Maternal cimetidine PK	Effects of time postpartum on cimetidine elimination rate constant	3-5 weeks, 3-4 months and 6-8 months postpartum
Secondary	Relationship between BCRP expression and activity	Effect of time postpartum on BCRP protein expression in MECs and correlation with cimetidine mammary CL	3-5 weeks, 3-4 months and 6-8 months postpartum