Relationship between antipyrine elimination rate constant, clearance and volume of distribution in the rat

While the relationship between the inverse of antipyrine half-life and clearance has been shown to be approximately linear in man, a recent report indicated that there was no significant relationship between antipyrine elimination rate constant (lambda) and clearance (CL) in the rat. Since this relationship is critical to the use of non-invasive methods to estimate drug metabolizing capacity, we have re-examined the relationship between lambda and CL in the rat. A significant correlation (r = 0.887) was found between antipyrine lambda and CL, while only a weak relationship (r = 0.442) was found between lambda and volume of distribution. These data support the use of non-invasive methods to estimate antipyrine elimination in the rat when invasive methods need to be avoided.