Drug Excretion in Breast Milk

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age14-50
SponsorUniversity of Washington

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Healthy postpartum women

18-50 years of age and their infants

Able to provide written informed consent

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Cimetidine 200 MG

    Drug

    Cimetidine will serve as the probe drug

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Healthy Lactating WomenOther 1 intervention

Trial outcomes

Primary outcomes

1

Mammary 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
2

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
3

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

Secondary outcomes

1

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
2

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
3

Maternal cimetidine PK

Effects of time postpartum on cimetidine CL/F

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

Maternal cimetidine PK

Effects of time postpartum on cimetidine renal CL

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Washington

Lead sponsor

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

Collaborator