WinNONLIN software

Pharmacokinetic Analysis. Standard noncompartmental analyses were conducted to assess ATI and ATF pharmacokinetics using WinNonlin software (v. 2.1) (Pharsight, Mountain View, CA). The areas under the plasma concentration versus time curve from time zero to inhnity (AUCint) were determined via the log-linear trapezoidal method. The terminal half-life was determined from the relationship of ti/2 = In 2/, where k is the negative slope of the terminal phase of the InC versus time plot. Systemic clearance (CL) was estimated by dividing the administered dose by AUCint. The volume of distribution at steady state (Vss) was determined by the product of clearance and the mean residence time. 

WinNonlin, Pharsight Corp., http //www.pharsight.com SAAM II, SAAM Institute, Inc., http //www.saam.com TOXICOKINETIC SOFTWARE... 

The pharmacokinetic values were calculated by the pharmacokinetics software WinNonlin, version 1.5. and were summarized in Table 1. 

Half-lives were calculated by the pharmacokinetics software WinNonlin, version 1.5. In case of the intravenous administration, a 2 compartmental model was chosen in case of oral administration, a non-compartmenal model. The AUCs were calculated using the linear trapezoidal rule. The results are summarized in Table 3. 

The pharmokinetic parameters in the blood, plasma, excreta and the kinetics in organs and tissues are calculated using an appropriate pharmacokinetics software (e.g. WinNonlin). 

The software system WinNonlin (18) uses a combination of the trapezoidal and log-trapezoidal formulas to estimate AUC and AUMC, and the formulas resulting from them. As a result, no statistical information is available. 

Microcomputers are also used to systematize, speed up formulation, simplify manufacturing processes, and reduce the number of needed bioavailability studies through simulated models and plasma level predictions. Commercially available software packages, such as WINNONLIN, SAS (Table 1), and other custom-designed programs, are generally used to solve the... 

Conventional PK models, which describe a concentration-time profile at a given dose, can be applied either using noncompartmental or compartmental analysis. The most commonly used software is WinNonlin from Pharsight. 

The validation process is outlined from writing user requirements specification to testing and validating specific analysis using estimation methods. This is followed with brief examples of validation approaches for some commonly encountered software, such as S-Plus , SAS , WinNonlin , and NONMEM . 

This ability is available in many software programs. NONMEM (Iconus, EUicott City, MD) has been widely used to estimate population models arising from both sparse and intensely sampled data. Other programs include WinNonMix (Pharsight Corp., Palo Alto, CA), Kinetica 2000 (Innaphase Corp, Philadelphia, PA), and Pop-Kinetics (SAAM Institute, Seattle, WA). ADAPT II and WinNonlin have focused on PK/PD models and have been combined with Bayesian approaches to estimate population models. 

The AIC used by Yamaoka et al. is not the exact AIC reported by Akaike but is slightly different. However, its use is valid if all the models under consideration all have the same log-likelihood function. Yamaoka et al. (1978) demonstrated the use of the AIC by distinguishing between mono-exponential, bi-exponential, and tri-exponential equations. However, not all software packages use this definition. For example, WinNonlin (Pharsight Corp., Cary NC) uses Eq. (1.45) with p equal to only the number of structural model parameters and does not include the estimated residual variance. SAAM II (SAAM Institute, Seattle, WA) calculates the AIC as... 

Heatherington, A., Vicini, P. and Golde, H. A pharmacoki-nctic/pharmacodynamic comparison of SAAM II and PC/ WinNonlin modeling software. Journal of Pharmaceutical Sciences 1998 87 1255-1263. 

Sample preparation for each compound is performed in 96 well plate using a semiautomatic liquid handing station. LC-MS/MS instrumentation is used for the quantification of the sample and the final raw data are stored. Further calculation is done by appropriate quantification application. From the quantification, data concentration of unknowm samples are extrated and plotted versus the sampling time points (average plasma concentration vs. time). Pharmacokinetic calculations are performed by using pharmacokinetic software WinNonlin Pharsight Corporation) ... 

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