In vitro evaluation of the plasma and blood compatibility of a parenteral formulation for ditekiren, a novel renin inhibitor pseudopeptide

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 p...

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Veröffentlicht in:Pharmaceutical research 1991-04, Vol.8 (4), p.475-479
Hauptverfasser: Greenfield, J C, Loux, S J, Sood, V K, Jenkins, K M, Davio, S R
Format: Artikel
Sprache:eng
Schlagworte:
Blood Proteins - drug effects
Buffers
Erythrocytes - drug effects
Hemolysis - drug effects
Humans
In Vitro Techniques
Oligopeptides - blood
Plasma
Platelet Aggregation - drug effects
Renin - antagonists & inhibitors
Solubility
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container_end_page 479
container_issue 4
container_start_page 475
container_title Pharmaceutical research
container_volume 8
creator Greenfield, J C
Loux, S J
Sood, V K
Jenkins, K M
Davio, S R
description 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.
doi_str_mv 10.1023/A:1015847027254
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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. 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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. 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subjects Blood Proteins - drug effects
Buffers
Erythrocytes - drug effects
Hemolysis - drug effects
Humans
In Vitro Techniques
Oligopeptides - blood
Plasma
Platelet Aggregation - drug effects
Renin - antagonists & inhibitors
Solubility
title In vitro evaluation of the plasma and blood compatibility of a parenteral formulation for ditekiren, a novel renin inhibitor pseudopeptide
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