Limited sampling model

Asai, G., Ando, Y., Saka, H., Ando, M., Sugiura, S., Sakai, S., Hasagawa, Y., and Shimokata, K. Estimation of the area under the concentration-time curve of carboplatin following irinotecan using a limited sampling model. European Journal of Clinical Pharmacology 1998 54 725-727. 

Ratain, M.J., Robert, J., and van der Vijgh, W.J.F. Limited sampling models for doxorubicin pharmacokinetics. Journal of Clinical Oncology 1991 9 871-876. 

Shen, M., Schilder, R.J., Obasaju, C., and Gallo, J.M. Population pharmacokinetic and limited sampling models for carboplatin administered in high dose combination regimens with peripheral blood stem cell support. Cancer Chemotherapy and Pharmacology 2002 50 243-250. 

The technique is not optimal the instrument response (Y) is a predictor of analyte values (X). The limitation for modeling is in the representation of calibration set chemistry, sample presentation, and unknown variations of instrument and operator during measurement. 

The real crystalline forms are generally intermediate between the limit-ordered and limit-disordered models, the amount of disorder being dependent on the condition of crystallization and thermal and mechanical treatments of the samples. A condition to have more or less disordered modifications, corresponding to the same unit cell, is the substantial equality of steric hindrances in the space regions where a statistical substitution is achieved (Figure 2.29b). 

Population PK/PD models, which in addition to the characterization of PK and PD, involve relationships between covariates (for instance, patient characteristics such as age, body weight) and PK/PD parameters, allow us to assess and to quantify potential sources of variability in exposure and response in specific target population, even under erratic and limited sampling conditions. Often implications of significant covariate effects can be evaluated by computer simulations using the population PK/PD model. 

Finally, the MOS should also take into account the uncertainties in the estimated exposure. For predicted exposure estimates, this requires an uncertainty analysis (Section 8.2.3) involving the determination of the uncertainty in the model output value, based on the collective uncertainty of the model input parameters. General sources of variability and uncertainty in exposure assessments are measurement errors, sampling errors, variability in natural systems and human behavior, limitations in model description, limitations in generic or indirect data, and professional judgment. 

Autosamplers take this same loop and valve principle and automate the filling and handle-turning sequence. The major differences between models on the market are in the way they get sample into the loop and the method of cleaning between injections. Most autoinjectors use a carousel loaded with sample valves to hold samples until their turn for injection occurs. Sample vials are usually capped with a screw cap fitted with a septum, although some recent autosamplers replace the carousel with microtiter plates having 96-364 wells containing the samples for use with robotic workstations. Conical vials are available for limited samples and 1-jUL injections are possible with some... 

It does not appear that any attempt has been made to couple this BKO model to a means by which to calculate the CDS components of solvation, and this limits the model s accuracy, especially for solvents like water, where the CDS terms are not expected to be trivial. For water as solvent, studies have appeared that surround the solute with some small to moderate number of explicit solvent molecules, with the resulting supermolecule treated as interacting with the surrounding continuum. 23,230 Although such a treatment has the virtue of probably making the calculation less sensitive to the now-large cavity radius, it suffers from the usual explicit-solvent drawbacks of the size of the system, the complexity of the hypersurface, and the need for statistical sampling. 

As in humans ethical constraints limit sampling sites to peripheral blood vessels, absorption cannot directly be estimated. Hence, the absorption rate (ka, fe0i) as calculated from peripheral plasma concentration data by compartmental or noncom-partmental models reflects rather an oral bioavailability rate, unless any gut wall and liver first-pass elimination is ruled out [112]. 

L. Nguyen, B. Tranchand, C. Pnozzo, and P. Variol, Population pharmacokinetics model and limited sampling strategy for intravenous vinorelbine derived from phase I clinical trials. Br J Clin Pharmacol 53 459-468 (2002). 

Of particular interest is the utility of population modeling when sampling is limited, as is often the case in pediatric studies. For example, etoposide toxicity and efficacy have been related to exposure. It was not reasonable to execute an intense sampling PK study in the pediatric population, therefore a limited sampling strategy was proposed and done. In each subject only two samples were collected—one at about 3 hours postdose and another 5.5 hours postdose. The approach was shown to be able to estimate PK parameters that had little bias (18). 

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