A physiologically based pharmacokinetics model for melatonin—Effects of light and routes of administration

Peng, Henry T.; Bouak, Fethi; Vartanian, Oshin; Cheung, Bob

doi:10.1016/j.ijpharm.2013.09.033

Cited by 21 publications

(14 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decreased peak melatonin concentration might be interpreted as the participants receiving inadequate blue light during the day, due to the lower blue light transmission of the blueblocking IOL compared with the neutral IOL, as previously suggested (Mainster 2006). With regard to the anticarcinogenic effect, this hypothesis is primarily based on in vitro studies showing an effect of melatonin on tumour cell growth rate (Hill & Blask 1988) and on interventional studies including cancer patients (Mills et al 2005) using very high dosages of up to 40 mg of exogenous melatonin that are not readily comparable to changes in the endogenous 24-hr melatonin secretion (Peng et al 2013). Theoretically, a significant difference could be introduced by variation of the kits used to determine melatonin concentration, but to avoid such problems samples from both groups had been run on the same kits simultaneously.…”

Section: Discussionmentioning

confidence: 99%

The effect of blue‐blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery

Brøndsted

Haargaard

Sander

et al. 2016

Acta Ophthalmologica

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of blue‐blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery

Brøndsted

Haargaard

Sander

et al. 2016

Acta Ophthalmologica

View full text Add to dashboard Cite

show abstract

“…This model was recently supplemented to include the PK of oral exogenous melatonin and phase-shifting effects via melatonin receptors in the SCN (Breslow et al, 2013). A more complex physiologically-based model of exogenous melatonin whole-body PK is also available (Peng et al, 2013). These models provide comprehensive tools to optimize melatonin administration and light exposure schedule and can incorporate patient-specific molecular features to personalize the resetting strategy.…”

Section: Cts Disruptionmentioning

confidence: 99%

Systems Chronotherapeutics

et al. 2017

View full text Add to dashboard Cite

Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are controlled by the circadian timing system. Thus, the tolerability of nearly 500 medications varies by up to fivefold according to circadian scheduling, both in experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved the circadian timing system as a function of drug timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated in randomized clinical trials, especially for cancer and inflammatory diseases. However, recent technological advances have highlighted large interpatient differences in circadian functions resulting in significant variability in chronotherapy response. Such findings advocate for the advancement of personalized chronotherapeutics through interdisciplinary systems approaches. Thus, the combination of mathematical, statistical, technological, experimental, and clinical expertise is now shaping the development of dedicated devices and diagnostic and delivery algorithms enabling treatment individualization. In particular, multiscale systems chronopharmacology approaches currently combine mathematical modeling based on cellular and whole-body physiology to preclinical and clinical investigations toward the design of patient-tailored chronotherapies. We review recent systems research works aiming to the individualization of disease treatment, with emphasis on both cancer management and circadian timing system–resetting strategies for improving chronic disease control and patient outcomes.

show abstract

“…These models can tease out the effects of drug or formulation properties on release in accordance to changes in the ADME processes. Peng et al successfully demonstrated how PBPK modeling could be utilized to predict the plasma concentration of melatonin, a compound with strong circadian rhythms [155]. This goal was achieved by de-lumping tissues (salivary and pineal gland) into individual compartments on the basis of strong circadian effects due to light.…”

Section: Model Parameterization For Special Populationsmentioning

confidence: 99%

“…This goal was achieved by de-lumping tissues (salivary and pineal gland) into individual compartments on the basis of strong circadian effects due to light. The model demonstrated how delivery of exogenous melatonin as a controlled release formulation could mimic the endogenous rhythms [155]. …”

Section: Model Parameterization For Special Populationsmentioning

confidence: 99%

Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine

Hartmanshenn

Scherholz

Androulakis

2016

J Pharmacokinet Pharmacodyn

View full text Add to dashboard Cite

Personalized medicine strives to deliver the ‘right drug at the right dose’ by considering inter-person variability, one of the causes for therapeutic failure in specialized populations of patients. Physiologically-based Pharmacokinetic (PBPK) modeling is a key tool in the advancement of personalized medicine to evaluate complex clinical scenarios, making use of physiological information as well as physicochemical data to simulate various physiological states to predict the distribution of pharmacokinetic responses. The increased dependency on PBPK models to address regulatory questions is aligned with the ability of PBPK models to minimize ethical and technical difficulties associated with pharmacokinetic and toxicology experiments for special patient populations. Subpopulation modeling can be achieved through an iterative and integrative approach using an adopt, adapt, develop, assess, amend, and deliver [(AAD)2] methodology. PBPK modeling has two valuable applications in personalized medicine: (1) determining the importance of certain subpopulations within a distribution of pharmacokinetic responses for a given drug formulation and (2) establishing the formulation design space needed to attain a targeted drug plasma concentration profile. This review article focuses on model development for physiological differences associated with sex (male vs. female), age (pediatric vs. young adults vs. elderly), disease state (healthy vs. unhealthy), and temporal variation (influence of biological rhythms), connecting them to drug product formulation development within the Quality by Design framework. Although PBPK modeling has come a long way, there is still a lengthy road before it can be fully accepted by pharmacologists, clinicians, and the broader industry.

show abstract

A physiologically based pharmacokinetics model for melatonin—Effects of light and routes of administration

Cited by 21 publications

References 97 publications

The effect of blue‐blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery

The effect of blue‐blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery

Systems Chronotherapeutics

Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine

Contact Info

Product

Resources

About