In vitro evaluation of the plasma and blood compatibility of a parenteral formulation for ditekiren, a novel renin inhibitor pseudopeptide.
Ditekiren (U-71038; Boc-Pro-Phe-N-MeHis-Leu-psi[CHOHCH2]-Val-Ile-(aminomethyl)pyridine ) is a potent renin inhibitor peptide and was formulated for clinical intravenous administration in acidified dextrose. This formulation of ditekiren was evaluated in vitro with human and monkey plasma as to its potential for forming a precipitate either of drug or of plasma proteins. Analysis by centrifugation showed that no drug precipitation occurred in plasma from either species at concentrations 25 times higher than anticipated in clinical studies. Results obtained by turbidimetry indicated that formulated ditekiren did not cause aggregation of human platelets or flocculation of proteins at concentrations approaching the solubility limit of the drug in plasma. Ditekiren or vehicle also caused no detectable lysis of red cells at concentrations representing 10 times the maximum clinical level. Therefore, ditekiren solutions as formulated are judged completely compatible with blood and plasma upon clinical intravenous administration.
Greenfield
J C
JC
Drug Metabolism Research, Upjohn Laboratories, Upjohn Company, Kalamazoo, Michigan 49007.
Loux
S J
SJ
Sood
V K
VK
Jenkins
K M
KM
Davio
S R
SR
D001798:Blood Proteins / Q000187:drug effects; D002021:Buffers; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000097:blood*; D010949:Plasma; D010974:Platelet Aggregation / Q000187:drug effects; D012995:Solubility; D000092502:Renin Inhibitors
D001798:Blood Proteins; D002021:Buffers; D009842:Oligopeptides; D000092502:Renin Inhibitors; C050898:ditekiren