Subcutaneous pharmacokinetics of the cardiac hormone vessel dilator

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 (s.c.) via osmotic pumps. The pharmacokinetics of s.c. administered vessel dilator have not been evaluated previously. In the present study, the pharmacokinetics of vessel dilator following s.c. bolus (ScB) or 3 h s.c. infusion (ScI) were compared with those following i.v. bolus (IvB) administration in male Fischer 344 rats. The half-life (t½ ) of vessel dilator after ScI, IvB and ScB was 54, 43 and 30 min, respectively. The tmax for vessel dilator after IvB, ScB and ScI administration was 1.5, 23 and 156 min, respectively, whereas the corresponding Cmax values were 3749, 887 and 471 ng/L (normalized against the dose used for ScB and IvB). The area under the curve (AUC0-∞ ) for vessel dilator was 1166, 880 and 1652 ng h/mL (normalized) following IvB, ScB and ScI administration, respectively. The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 L following IvB, ScB and SCI administration, respectively; corresponding clearance values were 1.69, 1.50 and 0.78 L/h, respectively. Plasma concentrations of vessel dilator after each of the three methods of administration mirrored their predicted concentration-time profiles. We conclude that vessel dilator administered via ScI has a significantly greater AUC and t½ and slowed clearance compared with IvB or ScB administration (P < 0.001), suggesting that s.c. infusion is the preferred method of administration, based on pharmacokinetics, to treat cancers.

Heart Peptide Hormones: Adjunct and Primary Treatments of Cancer

“…On the other hand, the treatment of congestive heart failure with vessel dilator in humans was via intravenous infusion (105). To determine which of these methods might be best for treating humans with cancer, pharmacokinetics were compared between intravenous bolus (IvB), subcutaneous bolus (ScB) and subcutaneous infusion for 3 hours in male Fischer 344 rats (106). The half lives of vessel dilator after ScI, IvB and ScB were 54, 43, and 30 minutes (106).…”

“…The half lives of vessel dilator after ScI, IvB and ScB were 54, 43, and 30 minutes (106). The time to reach peak concentrations in plasma (t max ) after IvB, ScB and ScI of vessel dilator was 1.5, 23, and 156 minutes (106). The peak plasma concentrations (C max ) withI ScI, IvB and ScB were 3749, 887, and 471 ng/l (normalized against the dose used for ScB and IvB) (106).…”

“…The time to reach peak concentrations in plasma (t max ) after IvB, ScB and ScI of vessel dilator was 1.5, 23, and 156 minutes (106). The peak plasma concentrations (C max ) withI ScI, IvB and ScB were 3749, 887, and 471 ng/l (normalized against the dose used for ScB and IvB) (106). The area under the curve (AUC) for vessel dilator was 1,166, 880, and 1,652 ng h/ml (normalized) following IvB, ScB and ScI administration (106).…”

“…The peak plasma concentrations (C max ) withI ScI, IvB and ScB were 3749, 887, and 471 ng/l (normalized against the dose used for ScB and IvB) (106). The area under the curve (AUC) for vessel dilator was 1,166, 880, and 1,652 ng h/ml (normalized) following IvB, ScB and ScI administration (106). The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 l following IvB, ScB and ScI administration, with its corresponding clearance being 1.69, 1.50 and 0.78 l/h, respectively (106).…”

“…The area under the curve (AUC) for vessel dilator was 1,166, 880, and 1,652 ng h/ml (normalized) following IvB, ScB and ScI administration (106). The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 l following IvB, ScB and ScI administration, with its corresponding clearance being 1.69, 1.50 and 0.78 l/h, respectively (106). Plasma concentrations of vessel dilator after each of these three methods of administration mirrored their predicted concentration profiles (106).…”