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BIOMD0000000241 - Shi1993_Caffeine_pressor_tolerance


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Reference Publication
Publication ID: 8422743
Shi J, Benowitz NL, Denaro CP, Sheiner LB.
Pharmacokinetic-pharmacodynamic modeling of caffeine: tolerance to pressor effects.
Clin. Pharmacol. Ther. 1993 Jan; 53(1): 6-14
Division of Clinical Pharmacology and Experimental Therapeutics, San Francisco General Hospital Medical Center, California 94110.  [more]
Original Model: BIOMD0000000241.xml.origin
Submitter: Lukas Endler
Submission ID: MODEL1001080000
Submission Date: 08 Jan 2010 17:53:04 UTC
Last Modification Date: 21 Jun 2011 12:46:00 UTC
Creation Date: 08 Jan 2010 11:00:59 UTC
Encoders:  Lukas Endler
set #1
bqbiol:isVersionOf Gene Ontology regulation of blood pressure
Gene Ontology response to caffeine
bqbiol:occursIn Taxonomy Homo sapiens

described in: Pharmacokinetic-pharmacodynamic modeling of caffeine: Tolerance to pressor effects
Shi J, Benowitz NL, Denaro CP and Sheiner LB. ; Clin. Pharmacol. Ther. 1993 Jan;53(1):6-14. PMID: 8422743 ;
We propose a parametric pharmacokinetic-pharmacodynamic model for caffeine that quantifies the development of tolerance to the pressor effect of the drug and characterizes the mean behavior and inter-individual variation of both pharmacokinetics and pressor effect. Our study in a small group of subjects indicates that acute tolerance develops to the pressor effect of caffeine and that both the pressor effect and tolerance occur after some time delay relative to changes in plasma caffeine concentration. The half-life of equilibration of effect with plasma caffeine concentration is about 20 minutes. The half-life of development and regression of tolerance is estimated to be about 1 hour, and the model suggests that tolerance, at its fullest, causes more than a 90 percent reduction of initial (nontolerant) effect. Whereas tolerance to the pressor effect of caffeine develops in habitual coffee drinkers, the pressor response is regained after relatively brief periods of abstinence. Because of the rapid development and regression of tolerance, the pressor response to caffeine depends on how much caffeine is consumed, the schedule of consumption, and the elimination half-life of caffeine.

Caffeine intake in this version is modelled as cups of coffee drunk at regular intervals (parameter t_interval ). The amount of caffeine per cup is determined by the parameter cupsize . The body weight of the person drinking is given by the parameter bodyweight .
The even coffee cup occures delayed to the drinking of each cup, as the availability of the caffeine in the digestive tract is assumed to be delayed to the ingestion by the time t_lag .

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The Team.
For more information see the terms of use .
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Publication ID: 8422743 Submission Date: 08 Jan 2010 17:53:04 UTC Last Modification Date: 21 Jun 2011 12:46:00 UTC Creation Date: 08 Jan 2010 11:00:59 UTC
Mathematical expressions
Rate Rule (variable: X_gut) Rate Rule (variable: C_p) Rate Rule (variable: C_per) Rate Rule (variable: C_e)
Rate Rule (variable: C_t) Assignment Rule (variable: MAP)    
coffee cup      
Physical entities
Compartments Species
Gut X_gut    
C C_p    
P C_per    
Tol C_t    
Eff C_e    
Global parameters
CL V_C k_a t_lag
k10 k12 k21 t_half
F k_eo k_tol E_0
S T_50 MAP t_intervall
cupsize bodyweight cups  
Reactions (0)
Rules (6)
 Rate Rule (name: X_gut) d [ X_gut] / d t= (-k_a)*X_gut
 Rate Rule (name: C_p) d [ C_p] / d t= k_a*F*X_gut/V_C-k12*C_p+k21*C_per-k10*C_p
 Rate Rule (name: C_per) d [ C_per] / d t= k12*C_p-k21*C_per
 Rate Rule (name: C_e) d [ C_e] / d t= k_eo*(C_p-C_e)
 Rate Rule (name: C_t) d [ C_t] / d t= k_tol*(C_p-C_t)
 Assignment Rule (name: E) MAP = E_0+S*C_e/(1+C_t/T_50)
Events (1)
 coffee cup
cups = cups+1
X_gut = X_gut+cupsize/bodyweight
 Gut Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: Gut
Initial amount: 0.0  (Units: mg_per_kg)
 C Spatial dimensions: 3.0  Compartment size: 0.31
Compartment: C
Initial amount: 0.0
 P Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: P
Initial concentration: 0.0
 Tol Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: Tol
Initial concentration: 0.0
 Eff Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: Eff
Initial concentration: 0.0
Global Parameters (19)
Value: 0.11
Value: 0.32   (Units: liter_per_kg)
Value: 12.0   (Units: per_hour)
Value: 0.15   (Units: hr)
Value: 0.34   (Units: per_hour)
Value: 1.64   (Units: per_hour)
Value: 1.19   (Units: per_hour)
Value: 3.98   (Units: hr)
Value: 0.984
Value: 2.03   (Units: per_hour)
Value: 0.75   (Units: per_hour)
Value: 83.3   (Units: mm_Hg)
Value: 19.07   (Units: mm_Hg per (mg/l))
Value: 0.26   (Units: mg/l)
Value: NaN   (Units: mm_Hg)
Value: 2.0   (Units: hr)
Value: 90.0   (Units: mg)
Value: 80.0   (Units: kilogram)
Representative curation result(s)
Representative curation result(s) of BIOMD0000000241

Curator's comment: (updated: 08 Jan 2010 18:01:14 GMT)

Simulation of the mean arterial pressure (MAP) when drinking cups of coffee at different time intervals as in fig. 5 of the original publication. The caffeine content of each cup was 90 mg, the assumed body weight 80 kg. The time courses were computed using SBML ODESolver (options for event detection: --printstep 500 -n)