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.