Psychopharmacology

, Volume 190, Issue 2, pp 201–211 | Cite as

Pharmacokinetic and behavioral characterization of a long-term antipsychotic delivery system in rodents and rabbits

  • Kayla L. Metzger
  • Jody M. Shoemaker
  • Jonathan B. Kahn
  • Christina R. Maxwell
  • Yuling Liang
  • Jan Tokarczyk
  • Stephen J. Kanes
  • Meredith Hans
  • Anthony M. Lowman
  • Nily Dan
  • Karen I. Winey
  • Neal R. Swerdlow
  • Steven J. Siegel
Original Investigation

Abstract

Rationale

Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel long-term delivery systems.

Objectives

The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits.

Materials and methods

Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits.

Results

Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits.

Conclusions

The current study suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a degree of reversibility not available with depot formulations.

Keywords

Antipsychotic agents Treatment adherence Schizophrenia Drug delivery systems Drug implants Prepulse inhibition Haloperidol Rat Mouse Rabbit 

Notes

Acknowledgements

The Stanley Medical Research Institute funded this research. Intellectual property related to haloperidol implants developed at the University of Pennsylvania is owned by the University. Research by NRS and JMS supported by MH42228 and MH01436. All experiments comply with “Principles of Laboratory Animal Care” and conform to University of Pennsylvania IACUC standards.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Kayla L. Metzger
    • 1
    • 2
  • Jody M. Shoemaker
    • 3
  • Jonathan B. Kahn
    • 1
    • 2
  • Christina R. Maxwell
    • 1
    • 2
  • Yuling Liang
    • 1
    • 2
  • Jan Tokarczyk
    • 2
  • Stephen J. Kanes
    • 2
  • Meredith Hans
    • 4
  • Anthony M. Lowman
    • 4
  • Nily Dan
    • 4
  • Karen I. Winey
    • 5
  • Neal R. Swerdlow
    • 3
  • Steven J. Siegel
    • 1
    • 2
  1. 1.Stanley Center for Experimental Therapeutics in Psychiatry, Translational Research LaboratoriesUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Neuropsychiatry, Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PsychiatryUniversity of CaliforniaSan DiegoUSA
  4. 4.Department of Chemical EngineeringDrexel UniversityPhiladelphiaUSA
  5. 5.Department of Materials Science and EngineeringUniversity of PennsylvaniaPhiladelphiaUSA

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