title: Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies.
abstract: Prazosin, an antihypertensive drug with postsynaptic alpha 1-adrenergic blocking activity, has been coupled to poly-N5-(3-hydroxypropyl-L-glutamine) (PHPG) via a carbamate linkage. PHPG was activated by p-nitrophenyl chloroformate and then reacted with prazosin to form p(HPG-prazosin carbamate) conjugate. Drug loading was 23.9% (w/w). Activated polymer and conjugates were characterized by infrared spectroscopy and differential scanning calorimetry. In vitro studies proceeded in pH 7.4 isotonic phosphate-buffered saline solution. Prazosin was released at a rate of 0.92 mg/day/100 mg conjugate from p(HPG-prazosin carbamate) particles. In vivo studies were performed with New Zealand White rabbits. P(HPG-prazosin carbamate) conjugate particles (100 mg) were suspended in 2 ml saline and injected subcutaneously into both flanks of rabbits. P(HPG-prazosin carbamate) conjugates, following an initial burst, demonstrated a nearly constant plasma prazosin concentration profile above 2 ng/ml, which was maintained for 10 days.
authors.affiliation: Department of Pharmaceutics, University of Utah, Salt Lake City 84108.
authors.forename: X L
authors.initials: XL
authors.lastname: Li
authors.forename: N W
authors.initials: NW
authors.lastname: Adams
authors.forename: D B
authors.initials: DB
authors.lastname: Bennett
authors.forename: J
authors.initials: J
authors.lastname: Feijen
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D006868:Hydrolysis; D008297:Male; D010455:Peptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011224:Prazosin / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits
chemical_list: D003692:Delayed-Action Preparations; D010455:Peptides; D011355:Prodrugs; C070258:poly-N(5)-(3-hydroxypropylglutamine)-prazosin carbamate; D011224:Prazosin