Hepatic drug clearance: the effect of age using indocyanine green as a model compound.

Abstract

The hepatic extraction ratio and clearance of indocyanine green (ICG) were determined and used to derive apparent liver blood flow in nine subjects between the ages of 22 and 83 years. There was no correlation between the hepatic extraction ratio of ICG and age (rs = -0.435, NS). There was a significant negative correlation between both ICG clearance and age (rs = -0.710, P < 0.05) and apparent liver blood flow and age (rs = -0.750, P < 0.05). These results validate the comparison of liver blood flow values derived from ICG clearance in humans over a wide age range and confirm that liver blood flow does fall with age.

Pharmacokinetics of trapidil, an antagonist of platelet derived growth factor, in healthy subjects and in patients with liver cirrhosis

“…The fact that we could The concentration-time curves of the terminal elimination phase of trapidil exhibited a slight convexity (see not detect a relationship between trapidil clearance and ICG clearance, the latter reflecting liver blood flow and inset of Figure 1a) which might reflect non-linear kinetics. Non-linear kinetics have already been suggested hence the decrease in the intrinsic clearance of a drug [14], is in accordance with the complete bioavailability from a single dose study with ascending oral doses, where the relative bioavailability of a 300 mg dose of trapidil without considerable first pass metabolism. The inverse correlation between the AUC of trapidil patients cannot be judged.…”

“…test [13], indocyaninegreen (ICG) clearance [ 14]. Demographic data of patients and controls in study II Trapidil is completely absorbed and does not undergo first-pass metabolism [ 10].…”

Age-dependency in the metabolism of flaxseed lignans by healthy adults

“…Consistent with this conclusion, there was no correlation of measured plasma enterolignans with age. This was surprising as increased age is often associated with changing gut microflora (Claesson et al, 2011;Enck et al, 2009;Flint et al, 2012;O'Toole & Claesson, 2010;Woodmansey, 2007) and reduced absorption and metabolism (Wynne et al, 1990). The ability for both younger and older participants to process flaxseed lignans similarly is encouraging in light of their suggested antioxidative and antitumourigenic benefits.…”

“…However, only in the older age group were END and ENL significantly greater than baseline values, despite a trend in the younger group. This may be attributed to the reduced sample size in this group, to agerelated differences in gut microflora (Woodmansey, 2007) or to the lower liver volume of elderly people compared to younger people (Wynne et al, 1990). This latter point may occur with drugs, like nutritional bioactives, which have increased presence in circulation of individuals ≥60 years of age compared to adults in their 20s, despite being administered equal doses of the same drug (Castleden & George, 1979;Kelly, McGarry, O'Malley, & O'Brien, 1982).…”

Diagnostic laboratory tests

“…The bromsulphalein (BSP) test is seldom performed now because of the possibility of an anaphylactic reaction. The indocyanine green (ICG) test is able to provide a good prediction of hepatic blood flow in healthy adults, but gives low readings in patients with liver cirrhosis, who show a marked decrease in extraction of ICG [16].…”