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 volunteersQualifiers
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
Sequential
Treatments tested in this trial
Cimetidine 200 MG
DrugCimetidine will serve as the probe drug
Treatment groups
Trial outcomes
Primary outcomes
Mammary clearance of cimetidine
Cimetidine excretion into breast milk at three postpartum stages
Mammary epithelial cell expression of BCRP
BCRP protein expression in MECs at three postpartum stages
Mammary epithelial cell expression of OCT1
OCT1 protein expression in MECs at three postpartum stages
Secondary outcomes
Cimetidine relative infant dose and infant concentration
cimetidine relative infant dose (RID) and infant concentration
Relationship between OCT1 expression and activity
Effect of time postpartum on OCT1 protein expression in MECs and correlation with cimetidine mammary CL
Maternal cimetidine PK
Effects of time postpartum on cimetidine CL/F
Maternal cimetidine PK
Effects of time postpartum on cimetidine renal CL
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