Drug Excretion in Breast Milk

NCT ID: NCT06056583

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-04
• Study Completion Date: 2028-09-30

Brief 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.

Detailed 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.

Conditions

Postpartum; Lactation; Drugs in Breast Milk; Mammary Drug Transporters; BCRP; OCT1

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Lactating Women

Healthy Lactating Women will be studied on 3 study days and serve as their own control.

Group Type: OTHER

Cimetidine 200 MG

Intervention Type: DRUG

Cimetidine will serve as the probe drug

Interventions

Cimetidine 200 MG

Cimetidine will serve as the probe drug

Intervention Type: DRUG

Other Intervention Names

Tagamet

Eligibility Criteria

Inclusion Criteria

1. Healthy postpartum women

2. 18-50 years of age and their infants

3. Able to provide written informed consent

Exclusion Criteria

1. Receiving cimetidine within the 3 days prior to each study day. Concomitant administration of cimetidine will confound interpretation of study results.

2. Hypersensitivity to cimetidine Patients with known allergic reactions to cimetidine will be excluded for safety reasons

3. Receiving medication known to interact with cimetidine: OCT, BCRP, CYP3A4, CYP2D6, CYP1A2 and CYP2C9 substrates (e.g. amiodarone, clopidogrel, diazepam, ketoconazole, metformin, nifedipine, phenytoin, procainamide, theophylline,tricyclic antidepressants and warfarin) Patients with drug interactions will be excluded for safety reasons.

4. Receiving BCRP inhibitors/inducers (afatinib, aripipraxole, axitinib, cimetidine, cyclosporine, curcumin/tumeric, delavirdine, efavirenz, elacridar, elvitegravir, etravirine, FTC, 5-fluorouracil, fluvastatin, imatinib, lanzoprazole, lapatinib, lopinavir, maraviroc, nelfinavir, nebicapone, nilotinib, novobiocin, oltipraz, omeprazole, pantoprazole, phenobarbital, promazine, rabeprazole, riboflavin, rifampicin, risperidone, saquinavir, sirolimus, sorafenib, sulfasalazine, sunitinib, tacrolimus, tariquidar, telaprevir, telatinib, teriflunomide, tolcapone, triflunomide, trametinib, trifluoperazine, venlafaxine, zidonuvir), OCT1 inhibitors/inducers (acyclovir, amantadine, amiloride, amitriptyline, bucindolol, carvedilol, chlorpheniramine, chlorpromazine, cimetidine, citalopram, clonidine, clopidogrel, clotrimazole, clozapine, cocaine, corticosterone, cyclosporine, daclatasvir, darunavir, desipramine, dextromethorphan, diltiazem, disopyramide, dronedarone, efavirenz, famotidine, fentanyl, fluvoxamine, formoterol, fuloxetine, griseofulvin, doxazosine, ganciclovir, guanfacine, imipramine, indinavir, isavuconazole, itraconazole, ketoconazole, lamotrigine, lasmiditan, levofloxacin, levomepromazine, lidocaine, maprotiline, methylnicotinamide, morphine, moxifloxacin, nefazodone, nelfinavir, nevirapine, nicotine, nomifensine, ondansetron, oxybutynin, paroxetine, pentamidine, phenoxybenzamine, prazosin, probenecid, procainamide, propafenone, pyrazinamide, quetiapine,quinidine, quinine, reboxetine, remoxidpride, reseripine, rifampicin, ritonavir, salmeterol, saquinavir, tramadol, trimethoprim, trimipramine, verapamil) Inhibitors and inducers of the drug transporters will confound data analysis and interpretation.

5. Kidney disease could confound data analysis and interpretation. Therefore, patients with known kidney disease with documented renal function impairment will be excluded from the study. Current serum creatinine > 1.2 mg/dL in their medical record will be excluded.

6. Known liver disease Liver disease will confound data analysis and interpretation. Therefore, patients with known significant liver disease will be excluded from the study. Current ALT exceeding 2-times the upper limit of normal in their medical record will be excluded.

7. Inability to fast for 4 hours prior to the study. To limit PK variability across study days, subjects will be requested to fast for 4 hours prior to each study day.

8. Smokers (tobacco or other nicotine containing products Nicotine interacts with OCT1 and will confound data analysis and interpretation

• Minimum Eligible Age: 14 Days
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Mary Hebert

Professor: Pharmacy; Adjunct Professor, Obstetrics & Gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary Hebert, PharmD, FCCP

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mary Hebert, PharmD, FCCP

Role: CONTACT

mhebert@uw.edu

206-616-5016

Facility Contacts

Mary F Hebert, PharmD

Role: primary

mhebert@uw.edu

206-616-5016

Other Identifiers

R01HD112282

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00018397

Identifier Type: -

Identifier Source: org_study_id