Development of an implantable infusion pump for sustained anti-HIV drug administration.
Factors such as insufficient drug potency, non-compliance and restricted tissue penetration contribute to incomplete suppression of Human Immunodeficiency Virus (HIV) and the difficulty to control this infection. Infusion via standard catheters can be a source of infection, which is potentially life threatening in these patients. We developed an implantable infusion pump, allowing to accommodate large volumes (16-50mL) of high viscous solutions (up to 23.96mPas at 39 degrees C) of anti-HIV agents and providing sustained release of medication: a standard Codman 3000 pump, which was initially developed to release aqueous solutions ( approximately 0.7mPas) into the spinal cord such as for pain medication, was transformed for release of viscous solutions up to 40mPas by adapting the diameter of the capillary flow restrictor, the capillary length and way of catheterisation--by placing the indwelling catheter in the vena cava. A pilot study of the pump implanted in 2 dogs showed continuous steady-state release of the protease inhibitor darunavir (25mg/dog/day administered for 25 days), thereby achieving plasma concentration levels of approximately 40ng/mL. Steady-state plasma levels were reproducible after monthly refill of the pumps. In conclusion, the implantable adapted Codman 3000 constant-flow infusion pump customized to anti-HIV therapy allows sustained release of anti-HIV medication and may represent an opportunity to reduce the pill burden and complexity of dosing schemes associated with common anti-HIV therapy.
Baert
Lieven
L
Chem-Pharm Development, Tibotec BVBA, Gen. De Wittelaan L11B 3, BE-2800 Mechelen, Belgium. lbaert@tibbe.jnj.com
Schueller
Laurent
L
Tardy
Yanik
Y
Macbride
Doug
D
Klooster
Gerben van't
Gv
Borghys
Herman
H
Clessens
Ellen
E
Van Den Mooter
Guy
G
Van Gyseghem
Elke
E
Van Remoortere
Pieter
P
Wigerinck
Piet
P
Rosier
Jan
J
D000465:Algorithms; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D000069454:Darunavir; D004285:Dogs; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood; D015918:Infusion Pumps, Implantable; D019999:Pharmaceutical Solutions; D010865:Pilot Projects; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood; D014783:Viscosity
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019999:Pharmaceutical Solutions; D013449:Sulfonamides; D000069454:Darunavir