Dosing regimens defined

Thus, the regimen would be a loading dose of 10.5 mg/ kg, followed by maintenance doses of 7.5 mg/kg every 5.41 hours. This regimen is not only impractical but, were it carried out, it would produce Cmax and Cmm concentrations too close to the limiting values to allow for any errors. A better approach would be to define clinicially relevant Cmax and Cm n values and use the approach in the previous section to develope a useful dosing regimen. 

None of the tested covariates was identified as having a clinically relevant impact on the PK of cetuximab. Thus, changes in dose or dosing regimen do not appear to be necessary in any of the subpopulations defined by these covariates. However, it should be noted that the majority of the studied patients had adequate hepatic and renal function. Overall, more than 90 % of the patients included in the PK database had normal hepatic function, more than 60% had normal renal function, and a further 32% had only mild impairment (creatinine clearance 50-80 mL/min). Hence, the effect of more severe renal or hepatic impairment on cetuximab PK remains to be elucidated. 

It depends on the target indication, e.g. acute or chronic use, and on the intended dosing regimen, e.g. once, twice or three-times daily, whether a given food effect is acceptable for justification of further development or if it defines the knock-out . 

Several animal model studies have focused on the immime response to infection and also to vaccination. Most studies identify antibody titer, but some also show cytokine production or possible mechanisms of bacterial evasion. A focus on immime response studies will help to further define B. anthracis pathogenesis and provide insight into the design of future vaccines and therapeutics. Most countermeasure studies have been conducted on vaccines, as antibiotic studies have typically been performed in vitro. Primary concerns are the length of required treatment, effieient prophylaxis methods, and less complicated dosing regimens for vaccines. In a theoretical bioterrorist attack scenario, it will be essential to distribute effective treatment and prophylaxis to infected or potentially exposed persons in an expedient manner. 

Given the potential mortality and known morbidity associated with febrile neutropenia, it may seem surprising that the routine use of TPMT genotyping in defining dose regimens for children with cancer did not gain early wide spread acceptance in the broader community of pediatric oncologists [15], There are several... 

Complex pharmacokinetic/pharmacodynamic (PK/PD) simulations are usually developed in a modular manner. Each component or subsystem of the overall simulation is developed one-by-one and then each component is linked to run in a continuous manner (see Figure 33.2). Simulation of clinical trials consists of a covariate model and input-output model coupled to a trial execution model (10). The covariate model defines patient-specific characteristics (e.g., age, weight, clearance, volume of distribution). The input-output model consists of all those elements that link the known inputs into the system (e.g., dose, dosing regimen, PK model, PK/PD model, covariate-PK/PD relationships, disease progression) to the outputs of the system (e.g., exposure, PD response, outcome, or survival). In a stochastic simulation, random error is introduced into the appropriate subsystems. For example, between-subject variability may be introduced among the PK parameters, like clearance. The outputs of the system are driven by the inputs... 

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