Population pharmacokinetic parameters

Sheiner LB, Beal SL. Evaluation of methods for estimating population pharmacokinetic parameters. II. Biexponential model and experimental pharmacokinetic data. / Pharmacokinet Biopharm 1981 9 635-51. 

Population pharmacokinetic parameters quantify population mean kineticS/ between-subject variability (intersubject variability)/ and residual variability. Residual variability includes within-subject variability/ model misspecification/ and measurement error. This information is necessary to design a dosage regimen for a drug. If all patients were identical/ the same dose would be appropriate for all. However/ since... 

Although population pharmacokinetic parameters have been estimated either by fitting all individuals data together as if there were no kinetic differences, or by fitting each individual s data separately and then combining the individual parameter estimates, these methods have certain theoretical problems that can only be aggravated when the deficiencies of typical clinical data are present. The nonlinear mixed-effect analysis avoids many of these deficiencies and... 

Vozeh S, Katz G, Steiner V, Eollath E. Population pharmacokinetic parameters in patients treated with oral mexiletine. Eur J Clin Pharmacol 1982 23 445-51. 

Naive Pooled Approach. The naive pooled approach, proposed by Sheiner and Beal, involves pooling all the data from all individuals as if they were from a single individual to obtain population parameter estimates.Generally, the naive pooled approach performs well in estimating population pharmacokinetic parameters from balanced pharmacokinetic data with small between-subject variations, but tends to confound individual differences and diverse sources of variability, and it generally performs poorly when dealing with imbalanced data. Additionally, caution is warranted when applying the naive pooled approach for PD data analysis because it may produce a distorted picture of the exposure-response relationship and thereby could have safety implications when applied to the treatment of individual patients. ... 

Steimer, J.L. Mallet, A. Golmard, J.L. Boisvieux, J.F. Alternative approaches to estimation of population pharmacokinetic parameters comparison with nonlinear mixed-effect model. Drug Metab. Rev. 1984,15 (1-2), 265-292. 

Sheiner, L.B. Beal, S.L. Evaluation of methods for estimating population pharmacokinetic parameters I. michaelis-menten model routine clinical data. J. Pharmacokinet. Biopharm. 1980, 8 (6), 553-571. 

The definitions and statistical theory of PPK, advantages, and disadvantages of PPK have been discussed in this chapter. Models, data type, methods, and software programs for estimating population pharmacokinetic parameters, design, and analysis of population pharmacokinetic studies have been reviewed, as well as its application in biopharmaceutics. The use of population methods continues to increase while there is a shortage of those who can implement the approach. 

Ette, E.I. Kelman, A.W. Howie, C.A. Whiting, B. Influence of interanimal variability on the estimation of population pharmacokinetic parameters in preclinical studies. Clin. Res. Reg. Affairs. 1994, 11, 121-139. 

Evaluates the biomedical literature to determine optimal therapeutic drug-monitoring strategies and population pharmacokinetic parameters. 

Here 0 is a vector of mean population pharmacokinetic parameters and Q is the variance-covariance matrix of between-subject random variability. Np represents a p-dimensional multivariate normal distribution, where p is the number of parameters. It is often more useful to consider the values of the parameters for the individual to be related to the population parameters via a covariate relationship, in which case the expression may be written as... 

TABLE 12.3 Population Pharmacokinetic Parameters of Investigational Drug... 

E. I. Ette, A. W. Kehnan, C. A. Howie, and B.Whiting, Interpretation of simnlation studies for efficient estimation of population pharmacokinetic parameters. Ann Phar-macother 27 1034-1039 and Correction 27 1548 (1993). 

N. M. Idkaidek, G. L. Amidon, D. E. Smith, N. M. Najib, and M. M. Hassan, Determination of the population pharmacokinetic parameters of sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium by simultaneous data fitting nsing NONMEM. Biopharm Drug Dispos 19 169-174 (1998). 

TABLE 15.2 Bootstrap Estimates for Various Population Pharmacokinetic Parameters Compared to the NONMEM Generated Parameters... 

A. Yafune and M. Ishiguro, Bootstrap approach for constrncting confidence intervals for population pharmacokinetic parameters II. A bootstrap modification of standard two stage method for phase I trial. Stat Med 18 601-612 (1999). 

Lindstrom, F.T. and Birkes, D.S. Estimation of population pharmacokinetic parameters using destructively obtained experimental data A simulation study of the 1-compartment open model. Drug Metabolism Reviews 1984 15 195-264. 

---