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Subcutaneous pharmacokinetics of the cardiac hormone vessel dilator
Author(s) -
Zhou Qingyu,
Whelan Glenn,
Zhou ShuFeng,
Lane Meghan L,
Vesely David L
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12266
Subject(s) - dilator , pharmacokinetics , medicine , bolus (digestion) , intravenous bolus , endocrinology
Summary 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 ( S c B ) or 3 h s.c. infusion ( S c I ) were compared with those following i.v. bolus ( I v B ) administration in male F ischer 344 rats. The half‐life (t ½ ) of vessel dilator after S c I , I v B and S c B was 54, 43 and 30 min, respectively. The t max for vessel dilator after I v B , S c B and S c I administration was 1.5, 23 and 156 min, respectively, whereas the corresponding C max values were 3749, 887 and 471 ng/L (normalized against the dose used for S c B and I v B ). The area under the curve ( AUC 0–∞ ) for vessel dilator was 1166, 880 and 1652 ng h/mL (normalized) following I v B , S c B and S c I administration, respectively. The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 L following I v B , S c B 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 S c I has a significantly greater AUC and t ½ and slowed clearance compared with I v B or S c B administration ( P < 0.001), suggesting that s.c. infusion is the preferred method of administration, based on pharmacokinetics, to treat cancers.