A population pharmacokinetic turnover and surge-function model for describing melatonin biological rhythm in healthy male subjects
✍ Scribed by Bruce Charles; Yvan Touitou; Brahim Selmaoui
- Book ID
- 102402181
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 297 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
A turnover model in combination with an empirical surge function based on a chromatographic peak detection algorithm was used to model the population pharmacokinetics of melatonin in 32 healthy males (aged 20-30 years, weight 62-85 kg) who had 15 blood samples drawn (11:00 to 08:00) on three occasions, separated by 2-4 weeks. Serum melatonin concentrations were measured by RIA. A pharmacokinetic model with a surge function was fitted to the data; dA/dt
Estimates were sought for the typical population parameter values and the intersubject variability (CV%) of; baseline amount of melatonin (A B ), elimination rate constant (K OUT ), peak amplitude (AMP), peak width (WID), acrophase (T 0 ). The model stability was validated using a nonparametric bootstrap (100 samples with replacement). Population typical values (CV%) were: A B ; 103 ng (103%), K OUT ; 0.255 h À1 (57.8%), AMP; 34.9 (108%), WID; 2.3 h (20.9%), T 0 ; 14.8 h (4.4%). Interoccasion variability (CV%) for; A B (12.3%), K OUT (29.5%) and AMP (9.1%) was much less than the corresponding intersubject variability. This approach has potential for application in clinical studies designed to characterize abnormal melatonin rhythms.