Urinary 6-hydroxymelatonin sulfate excretion in intellectually disabled subjects with sleep disorders and multiple medications: validation of measurements in urine extracted from diapers.
The aim of this study was to examine the applicability of urinary 6-hydroxymelatonin sulfate (MT6s) measurements in the evaluation of melatonin secretion in intellectually disabled patients with sleep disorders. All 17 patients received drugs with potential interactions with melatonin metabolism. Serum melatonin 24-h profiles were determined at hourly intervals. The area under the curve (AUC) value, peak amplitude, half-rise time, and half-decline time were calculated individually. Urinary MT6s excretion was determined from samples collected from disposable diapers during three consecutive days at varying intervals. The average excretion rate for each hour of the day was calculated. The excretion profiles were characterized by total amount of MT6s excretion/24 h/kg body mass, amount of excreted MT6s during 6 h of maximum excretion (MAX 6h), and start time of the maximum excretion (start MAX 6h). There were significant positive correlations between serum melatonin AUC value and total excretion of MT6s/body mass, between serum melatonin amplitude and urinary MAX 6h, and between melatonin half-rise time and start MAX 6h; one patient on phenobarbital medication was out of line. The serum melatonin profiles of the patients were classified by comparing them with those of matched healthy volunteers (low-, normal-, or high secretors, normal or delayed rhythm). Similarly, the parameters of MT6s profiles were compared with those obtained from healthy controls, and the patients were reclassified as normal or aberrant. The classifications based on serum melatonin and urinary MT6s measurements were mostly concordant. The daily pattern of urinary MT6s excretion reliably reflected the phase of the serum melatonin rhythm irrespective of the medications, but in some cases, the total amount of excreted MT6s was lower than expected based on serum melatonin measurements.
Laakso
M-L
ML
Sleep Research Centre, Rinnekoti Foundation, Espoo, Finland. Maija-Liisa.Laasko@rinnekoti.fi
Lindblom
N
N
Kaipainen
P
P
Kaski
M
M
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology; D065729:Cytochrome P-450 CYP2C9; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000652:urine; D008875:Middle Aged; D012893:Sleep Wake Disorders / Q000652:urine*
C054513:6-sulfatoxymelatonin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D008550:Melatonin