PMID- 24120727
OWN - NLM
STAT- MEDLINE
DCOM- 20140619
LR  - 20131118
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 458
IP  - 1
DP  - 2013 Dec 15
TI  - A physiologically based pharmacokinetics model for melatonin--effects of light 
      and routes of administration.
PG  - 156-68
LID - S0378-5173(13)00879-X [pii]
LID - 10.1016/j.ijpharm.2013.09.033 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) models were developed using MATLAB 
      Simulink((R)) to predict diurnal variations of endogenous melatonin with light as 
      well as pharmacokinetics of exogenous melatonin via different routes of 
      administration. The model was structured using whole body, including pineal and 
      saliva compartments, and parameterized based on the literature values for 
      endogenous melatonin. It was then optimized by including various intensities of 
      light and various dosage and formulation of melatonin. The model predictions 
      generally have a good fit with available experimental data as evaluated by mean 
      squared errors and ratios between model-predicted and observed values considering 
      large variations in melatonin secretion and pharmacokinetics as reported in the 
      literature. It also demonstrates the capability and usefulness in simulating 
      plasma and salivary concentrations of melatonin under different light conditions 
      and the interaction of endogenous melatonin with the pharmacokinetics of 
      exogenous melatonin. Given the mechanistic approach and programming flexibility 
      of MATLAB Simulink((R)), the PBPK model could provide predictions of endogenous 
      melatonin rhythms and pharmacokinetic changes in response to environmental 
      (light) and experimental (dosage and route of administration) conditions. 
      Furthermore, the model may be used to optimize the combined treatment using light 
      exposure and exogenous melatonin for maximal phase advances or delays.
CI  - Crown Copyright (c) 2013. Published by Elsevier B.V. All rights reserved.
FAU - Peng, Henry T
AU  - Peng HT
AD  - Defence Research and Development Canada - Toronto, 1133 Sheppard Avenue West, 
      Toronto, Ontario, Canada M3K 2C9. Electronic address: henry.peng@drdc-rddc.gc.ca.
FAU - Bouak, Fethi
AU  - Bouak F
FAU - Vartanian, Oshin
AU  - Vartanian O
FAU - Cheung, Bob
AU  - Cheung B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131011
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Chemistry, Pharmaceutical/methods
MH  - Light
MH  - Melatonin/*administration & dosage/*pharmacokinetics
MH  - Models, Biological
OTO - NOTNLM
OT  - Circadian rhythms
OT  - Light
OT  - MATLAB Simulink((R))
OT  - Melatonin
OT  - PBPK
OT  - Pharmacokinetics
EDAT- 2013/10/15 06:00
MHDA- 2014/06/20 06:00
CRDT- 2013/10/15 06:00
PHST- 2013/06/07 00:00 [received]
PHST- 2013/09/17 00:00 [revised]
PHST- 2013/09/24 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2014/06/20 06:00 [medline]
AID - S0378-5173(13)00879-X [pii]
AID - 10.1016/j.ijpharm.2013.09.033 [doi]
PST - ppublish
SO  - Int J Pharm. 2013 Dec 15;458(1):156-68. doi: 10.1016/j.ijpharm.2013.09.033. Epub 
      2013 Oct 11.