TITLE:
Population Pharmacokinetic Pharmacodynamic Modeling of Caffeine Using Visual Analogue Scales
AUTHORS:
Rebecca N. Burns, Ayyappa Chaturvedula, David C. Turner, Hailing Zhang, Chad M. Van Den Berg
KEYWORDS:
Caffeine; Population Pharmacokinetics; Population Pharmacodynamics; NONMEM®; Visual Analogue Scale
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.4,
April
28,
2014
ABSTRACT: Caffeine
is a commonly ingested psychoactive substance which affects alertness and
cognition. A clinical study was conducted to determine the effect of orally
ingested caffeine on visual analogue scale (VAS) responses in healthy, moderate
caffeine-consuming volunteers through the use of population
pharmacokinetic-pharmacodynamic (PK-PD) modeling. Twelve subjects were recruited
for a three-period cross-over study which utilized caffeine containing beverages.
Each visit included 8-hour blood plasma and VAS response collection for PK and
PD assessment respectively. The VAS used in the study, also called the caffeine
analog scale, has been previously validated for caffeine. Population PK-PD
modeling was conducted with NONMEM 7.2. Simultaneous and sequential modeling of
PK-PD was attempted. Final model selection was based on parameter estimate
precision, diagnostic plots, and visual predictive check (VPC) plots. Results
showed that a one-compartment open model with first-order absorption and
elimination best described the pharmacokinetics of caffeine. Sequential PK-PD
modeling was successful and an effect compartment model with linear slope and
baseline parameter best described caffeine pharmacodynamics. Diagnostic plots
showed no major bias and VPC plots showed agreement between observations and
predictions. The model was able to link VAS responses to caffeine concentration
in healthy volunteers and may be useful in clinical trial simulations and
design.