Population Pharmacokinetics/Pharmacodynamics

Population pharmacokinetics (PopPk) is the study of variability in plasma concentrations between and within individuals. It helps in identifying the demographic, pathophysiological, environmental and drug related factors that contribute to the variability observed in safety and efficacy of a drug. Unlike traditional PK studies where healthy volunteers are subjected to intensive sampling to determine PK parameters, PopPk studies offer an advantage of estimating PK parameters in target patient population with sparse sampling methodology. PopPK uses a nonlinear mixed effects modeling (NONMEM) approach. Variability in NONMEM is characterized in terms of fixed and random effects. The fixed effects are population average values of pharmacokinetic parameters such as clearance & volume of distribution, that may in turn be a function of patient characteristics. The random effects quantify the variability that is not explained by the fixed effects. These random effects include inter-subject, intra-subject, inter-occasion and residual variability. This methodology has also been extended to model population pharmacokinetic/pharmacodynamics (Pop PK/PD) relationships. This NONMEM approach was introduced by Lewis Sheiner and Stuart Beal approximately 30 years back. It has now become an integral part of drug development in industries and FDA review process.

Some of the softwares that have been used for modeling are as follows
NONMEM (most widely used)
ADAPT
Monolix
NPEM
NPAG (USC*PACK)
WinNonmix
Kinetica
SAS (PROC NLMIXED)
Splus

Pop PK/PD has led to a new discipline known as pharmacometrics. Barrett et al in J Clin Pharmacol 2008;48:632-649 define “Pharmacometrics” as that branch of science concerned with mathematical models of biology, pharmacology, disease, and physiology used to describe and quantify interactions between xenobiotics and patients, including beneficial effects and side effects resultant from such interfaces. So if you are a pharmacist, pharmacologist, statistician or biomedical engineer with good understanding of pharmacokinetics, pharmacodynamics, biological sciences, statistical and computational tools, you have a good chance to become a pharmacometrician. They are paid well both in the industry and the FDA. Infact, FDA has its own pharmacometrics group headed by Joga Gobburu and are promoting the use of modeling & simulation in drug development.

Are you a pharmacometrician or a PK/PD scientist? Is there a specific software that you use to model the data?