ISSN:
1573-904X
Keywords:
relaxin
;
pharmacokinetics
;
metabolism
;
protein
;
mass spectrometry
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Two forms of chemically synthesized human relaxin (hRlx and hRlx-2) were administered as 88 µg/kg intravenous bolus doses to pregnant and nonpregnant rhesus monkeys. No significant differences in pharmacokinetics were observed between pregnant and nonpregnant animals for either form of relaxin; however, clearance of hRlx (3.1–3.4 ml/min/kg) was significantly slower than clearance of hRlx-2 (6.2–6.5 ml/min/kg) in both pregnant and nonpregnant animals. Although the terminal half-lives for hRlx and hRlx-2 were similar (148–157 min), the initial and steady-state volumes of distribution were somewhat larger for hRlx-2 (71–85 and 398–418 ml/kg, respectively) than for hRlx (61–65 and 294–319 ml/kg, respectively). The metabolism of hRlx-2 was also investigated in pregnant and non-pregnant rhesus monkeys after iv bolus (0.44 mg/kg) or 60-min infusion (1.1 mg/kg) administration. Fast atom bombardment mass spectral analysis of the relaxin immunoreactivity isolated from the plasma indicated that hRlx-2 was partially degraded by removal of amino acids from the C terminus of the B chain. The percentage of intact material declined over a 60-min time course. At 60 min post-dose, intact hRlx-2 was ∼46–64% of the detected material. Degraded forms representing loss of one and four amino acids (hRlx) from the C terminus of the B chain were ∼11–13 and ∼19–34% of the detectable material, respectively.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015861108966
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