Drug Excretion in Breast Milk

NCT06056583 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: STUDY00018397R01HD112282
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

breast milk; lactation; cimetidine; proteomics; OCT1; BCRP; OCTN2; PEPT2; ENT1; CNT3; MRP1; OATP2B1; OATP3A1; OCT2; postpartum; pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Mammary clearance of cimetidine

  Cimetidine excretion into breast milk at three postpartum stages

  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

  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

  3-5 weeks, 3-4 months and 6-8 months postpartum

Secondary Outcomes (13)

• Cimetidine relative infant dose and infant concentration

  3-5 weeks, 3-4 months and 6-8 months postpartum

• Relationship between OCT1 expression and activity

  3-5 weeks, 3-4 months and 6-8 months postpartum

• Maternal cimetidine PK

  3-5 weeks, 3-4 months and 6-8 months postpartum

• Maternal cimetidine PK

  3-5 weeks, 3-4 months and 6-8 months postpartum

• Maternal cimetidine PK

  3-5 weeks, 3-4 months and 6-8 months postpartum

Study Arms (1)

Healthy Lactating Women

OTHER

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

Drug: Cimetidine 200 MG

Interventions

Cimetidine 200 MG DRUG

Cimetidine will serve as the probe drug

Also known as: Tagamet

Healthy Lactating Women

Eligibility Criteria

• Age: 14 Days - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy postpartum women
• years of age and their infants
• Able to provide written informed consent

You may not qualify if:

• Receiving cimetidine within the 3 days prior to each study day. Concomitant administration of cimetidine will confound interpretation of study results.
• Hypersensitivity to cimetidine Patients with known allergic reactions to cimetidine will be excluded for safety reasons
• 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.
• 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.
• 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.
• 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.
• 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.
• Smokers (tobacco or other nicotine containing products Nicotine interacts with OCT1 and will confound data analysis and interpretation

Sponsors & Collaborators

• University of Washington: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

MeSH Terms

Conditions

Breast Feeding

Interventions

Cimetidine

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mary Hebert, PharmD, FCCP

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary Hebert, PharmD, FCCP

CONTACT

206-616-5016; mhebert@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor: Pharmacy; Adjunct Professor, Obstetrics & Gynecology

Model Details: This is a phase 1 study design of an approved drug to evaluate the time-course for the expression and activity of OCT1 and BCRP in the mammary gland 3-5 weeks, 3-4 months and 6-8 months postpartum.

Study Record Dates

• First Submitted: September 14, 2023
• First Posted: September 28, 2023
• Study Start: December 4, 2023
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: After peer review and publication of data.
• Access Criteria: We are committed to share data with the academic community and researcher-at-large. We will adhere to the NIH Grant Policy on Sharing Research Data and Resources. That is, after final data collection and analysis and after full peer review is performed on our data, the de-identified data generated by this project will be made available when requested by the academic community and researchers-at-large contingent upon Material Transfer Agreements with the University of Washington.

Locations

US (1)