Predicting the Onset of Nonlinear Pharmacokinetics.
CPT Pharmacometrics Syst Pharmacol
; 7(10): 670-677, 2018 10.
Article
in En
| MEDLINE
| ID: mdl-30196577
ABSTRACT
When analyzing the pharmacokinetics (PK) of drugs, one is often faced with concentration C vs. time curves, which display a sharp transition at a critical concentration Ccrit . For C > Ccrit , the curve displays linear clearance and for C < Ccrit clearance increases in a nonlinear manner as C decreases. Often, it is important to choose a high enough dose such that PK remains linear in order to help ensure that continuous target engagement is achieved throughout the duration of therapy. In this article, we derive a simple expression for Ccrit for models involving linear and nonlinear (saturable) clearance, such as Michaelis-Menten and target-mediated drug disposition (TMDD) models. Study Highlights.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pharmacokinetics
/
Nonlinear Dynamics
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
CPT Pharmacometrics Syst Pharmacol
Year:
2018
Document type:
Article
Affiliation country:
Estados Unidos