A population pharmacokinetic turnover and surge-function model for describing melatonin biological rhythm in healthy male subjects

Charles, B. G., Touitou, Y. and Selmaoui, B. (2009) A population pharmacokinetic turnover and surge-function model for describing melatonin biological rhythm in healthy male subjects. Journal of Pharmaceutical Sciences, 98 2: 782-790. doi:10.1002/jps.21407


Author Charles, B. G.
Touitou, Y.
Selmaoui, B.
Title A population pharmacokinetic turnover and surge-function model for describing melatonin biological rhythm in healthy male subjects
Journal name Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0022-3549
Publication date 2009-02-01
Year available 2008
Sub-type Article (original research)
DOI 10.1002/jps.21407
Open Access Status DOI
Volume 98
Issue 2
Start page 782
End page 790
Total pages 9
Editor R. T. Borchardt
Place of publication New Jersey, U.S.A.
Publisher Wiley InterScience
Language eng
Subject C1
111504 Pharmaceutical Sciences
970106 Expanding Knowledge in the Biological Sciences
Abstract 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 = KIN [1 + (AMP/(((t - T0)/WID)N + 1))] - KOUT A, using NONMEM. Estimates were sought for the typical population parameter values and the intersubject variability (CV%) of; baseline amount of melatonin (AB), elimination rate constant (KOUT), peak amplitude (AMP), peak width (WID), acrophase (T0). The model stability was validated using a nonparametric bootstrap (100 samples with replacement). Population typical values (CV%) were: AB; 103 ng (103%), KOUT; 0.255 h-1 (57.8%), AMP; 34.9 (108%), WID; 2.3 h (20.9%), T0; 14.8 h (4.4%). Interoccasion variability (CV%) for; AB (12.3%), KOUT (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. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:782-790, 2009
Keyword Chemistry, Medicinal
Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Pharmacology & Pharmacy
Chemistry
CHEMISTRY, MEDICINAL
CHEMISTRY, MULTIDISCIPLINARY
PHARMACOLOGY & PHARMACY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Pharmacy Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 28 Mar 2009, 01:39:58 EST by Elizabeth Pyke on behalf of School of Pharmacy