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Subcutaneous Pharmacokinetics of the Cardiac Hormone Vessel Dilator

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Clinical and Experimental Pharmacology and Physiology

Published online on

Abstract

Vessel dilator, a hormone synthesized in the heart, eliminates 71% of human small‐cell lung cancers and 67% of human breast cancers growing in mice when given subcutaneously via osmotic pumps. The pharmacokinetic evaluation of subcutaneously administered vessel dilator has never been performed. Pharmacokinetics of A) administering vessel dilator by a subcutaneous bolus(ScB), B) via a 3‐hour subcutaneous infusion (ScI) were compared with C) an intravenous(IV) bolus in male Fischer 344 rats. Half‐life (t½) of vessel dilator via ScI was 54 minutes while IV and ScB t1/2 were 43 and 30 minutes. tmax for vessel dilator via IV, ScB, and ScI were 1.5, 23 and 156 minutes while Cmax for vessel dilator was 3749, 887 and 471 ng/L (normalized) for IV, ScB and ScI. Area under the curve (AUC0‐∞) (ng h/mL) for vessel dilator was 1166, 880, and 1652 (normalized) for IV,ScB and ScI, respectively. The volume of distribution (L) for vessel dilator was 2.38, 0.92 and 1.08 for IV, ScB and SCI. Clearance was 1.69, 1.50 and 0.78 L/h for IV, ScB and SCI,. The plasma concentrations of vessel dilator after each of the 3 methods of treatment mirrored their predicted concentration‐time profiles. We conclude that vessel dillator via ScI but as a significantly greater AUC, t½ and slowed clearance compared to IV or ScB (P < 0.001), suggesting it is the preferred method based upon pharmacokinetics to treat cancers. This article is protected by copyright. All rights reserved.