Melatonin Serum Levels and Metabolic Clearance Rate in Patients with Liver Cirrhosis

Abstract

To evaluate the influence of changes in liver function on serum levels of melatonin, we measured serum levels and MCR of the hormone in patients with liver cirrhosis and in healthy control subjects. Daytime (0900-1100 h) serum levels of melatonin in patients with liver cirrhosis were significantly elevated compared to those in healthy subjects. Significant positive correlations of the daytime serum levels of melatonin with the serum retention rate of indocyanine green dye and serum levels of total bilirubin were noted. The clearance of melatonin from blood showed a biphasic first-order kinetic pattern. The half-life of each phase was significantly prolonged in patients with cirrhosis compared to healthy subjects. Our data indicate that the elevated daytime serum levels of melatonin in patients with liver cirrhosis are due to decreased clearance, probably related to decreased liver blood flow, lowered activity of 6 beta-hydroxylase, and competition with bilirubin in the intrahepatic transport system.

On the Origin and the Consequences of Circadian Abnormalities in Patients With Cirrhosis

“…As melatonin is metabolized in the liver, it has been hypothesized that circadian sleep regulation might be implicated. Indeed, certain reported abnormalities, including high day-time plasma melatonin concentrations (9,10), low urinary aMT6s concentrations (11) and a reduction in the clearance of exogenously administered melatonin (12), support this hypothesis. However, other reported abnormalities, for example delays in the nocturnal rise of plasma melatonin and in its time to peak (9, 13), can not be explained by impairment of hepatic metabolism but might indicate dysfunction of the central circadian clock, and hence circadian timing.…”

The Physiology and Pharmacology of Melatonin in Humans

“…However, since plasma MLT displays a quick turnover (after i.v. bolus administration, plasma MLT displays a biexponential decay with a first distribution half-life of 2 min and a second metabolic half-life of 20 min), the absence of such a relationship could be the consequence of a blood sampling not short enough and would require reinvestigation [4, 5]. …”

Influence of Bright Light during Daytime on Sleep Parameters in Hospitalized Elderly Patients.

“…: 1, 6, 7) of seven melatonin secretions did not respond to diurnal bright light exposure, because two (ID. : 1,7) of the three patients were 77 yrs old, reflecting a probable agedependent functional change (Iguchi et al, 1982;Korf et al, 1998). The reason why melatonin in the remaining patient (ID.…”