Pharmacokinetic Study Comparing Topical, Rectal, and Oral Quetiapine

Mayo Clinic

Status and phase

Completed

Phase 1

Conditions

Delirium

Dementia

Treatments

Drug: Quetiapine 25 mg rectal suppository

Drug: Quetiapine 25 mg tablet by mouth

Drug: Quetiapine 25 mg gel applied topically

Study type

Interventional

Funder types

Other

Identifiers

NCT02131545

14-000896

Details and patient eligibility

About

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.

Enrollment

10 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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