Pharmacokinetic Study Comparing Topical, Rectal, and Oral Quetiapine

Study Overview
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Brief Summary
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Quetiapine, a second generation antipsychotic, is only available as oral tablets. However, topical and rectal formulations have been produced in compounding pharmacies. There is no data available suggesting that topical or rectal formulations provide serum levels similar to oral medication. In the clinical setting, when oral administration of quetiapine is not possible (for example, when a patient is extremely ill physically or mentally or both), clinicians and pharmacists have collaborated in such cases and have at times had to administer quetiapine compounded in other dosage formulations such as rectal or topical formulations. Despite clinical effectiveness of these other formulations, there are no available studies that have investigated blood levels of the drug other than the oral form. The investigators are therefore designing this pharmacokinetic study to evaluate the the systemic absorption of quetiapine in oral, rectal and topical formulations. If the investigators are able to demonstrate detectable levels from rectal and topical quetiapine formulations compared to the oral form, this knowledge will enhance clinical psychiatric practice by providing a more broad route of administration for quetiapine which is a commonly used drug for psychiatric symptoms.

Official Title
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A Single Dose Pharmacokinetic Study of Topical and Rectal Quetiapine Compared to Oral Quetiapine in Healthy Adults

Conditions
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Dementia, Delirium

Intervention / Treatment
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* Drug: Quetiapine 25 mg gel applied topically
* Drug: Quetiapine 25 mg tablet by mouth
* Drug: Quetiapine 25 mg rectal suppository
* Drug: Quetiapine 25 mg gel applied topically


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult volunteers (18-65 years old) willing to undergo a general health screen consisting of blood pressure, heart rate, respiratory rate, height, weight, temperature, and electrocardiogram will be identified. The below parameters must be met to be consider an adult healthy to volunteer for inclusion in this study: Blood pressure less than 160/99 mmHg and greater than 105/50 mmHg Heart rate between 50-100 beats per minutes Respiratory rate between 10-30 breaths per minute Temperature between 34 °C and 37.5°F Corrected QT interval of < 470 msec Liver function tests less than 1.5 times the upper limit of normal Estimated creatinine clearance (estimated by Cockcroft Gault formulation) greater than 60 mL/min Female participants will complete a urine pregnancy test that must result in a negative finding Exclusion: Allergy to quetiapine, Lipoderm or polyethylene glycol Currently taking quetiapine Pregnant, planning to become pregnant or breast feeding Over or under 30% of ideal body weight History of or active cardiovascular disease (except hypertension meeting the inclusion criteria for blood pressure), severe kidney disease (i.e. needing dialysis), or liver disease History of schizophrenia, bipolar disorder, substance use disorders (but excluding nicotine use disorders and stable unipolar depression (See below)) Unstable unipolar depression, defined as hospitalization for depression within 1 year or changes to an antidepressant regimen within 6 months History of seizure or seizure disorder Parkinson's disease, Huntington's disease, tardive dyskinesia or other diagnosed movement disorder History of/or active hematologic/oncologic illness Dementia Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome History of organ transplant History of gastric bypass Contraindications for suppository administration With Ostomy, chronic diarrhea Diabetes, type 1 or type 2 Prolong corrected QT interval (>470 msec) or history of congenital long QT syndrome Open wound(s) or unhealed wound(s) at topical medication application site (anterior forearm) Active or latent tuberculous and currently prescribed pharmacotherapy treatments Currently prescribed or taken with in the last 7 days, medications which have a known interaction with quetiapine or compound the risk of adverse events associated with quetiapine: QTc prolonging medications: Antipsychotics Vaughan Williams Class IA, IB, IC, III antiarrhythmics Anti-infective agents (excluding topical agents, oral penicillins, oral cephalosporins) Antiemetics Methadone Cisapride Cimetidine Divalproex sodium/valproic acid Tetrabenazine Solifenacin Tricyclic antidepressants Tizanidine Fingolimod Increase quetiapine concentrations, not previously mentioned Paroxetine Fluoxetine Fluvoxamine Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) Tamoxifen Cyclosporin (excluding ophthalmic formulation) Nefazodone Decrease quetiapine levels, not previously mentioned Bosentan Carbamazepine Glucocorticoids Modafinil Primidone St. John's wort Barbiturates Phenytoin Vulnerable populations will be excluded (i.e. prisoners, wards of the state, emancipated minors, children, pregnant women) Inability to receive telephone calls for the purpose of post-intervention follow-up Inability or unwillingness of individual to give written informed consent Non-English speaking populations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine<br>Quetiapine 25 mg | Drug: Quetiapine 25 mg gel applied topically<br>* Quetiapine 25 mg gel applied topically; 9 serum quetiapine levels drawn over the course of 8 hours<br>* Other names: Seroquel;Drug: Quetiapine 25 mg tablet by mouth<br>* Quetiapine 25 mg tablet administered by mouth; 9 serum quetiapine levels drawn over the course of 8 hours<br>* Other names: Seroquel;Drug: Quetiapine 25 mg rectal suppository<br>* Quetiapine 25 mg suppository administered rectally; 9 serum quetiapine levels drawn over the course of 8 hours<br>* Other names: Quetiapine;Drug: Quetiapine 25 mg gel applied topically<br>* Quetiapine 75 mg gel applied topically every 4 hours for 24 hours; 6 serum quetiapine levels drawn over the course of 24 hours<br>* Other names: Seroquel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum quetiapine levels after topical application (Visit 1) | Areas under the curve versus time | 8 hours | 
| Serum quetiapine levels after oral administration (Visit 2) | Areas under the curve versus time | 8 hours (no sooner than 72 hours from end of visit 1) | 
| Serum quetiapine levels after rectal administration (Visit 3) | Areas under the curve versus time | 8 hours (no sooner than 72 hours from end of visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum quetiapine levels after topical administration over 24 hours | Topical quetiapine applied every 4 hours for 24 hours | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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quetiapine, pharmacokinetics, dementia, delirium, palliative care