![nonmem 7 tutorial nonmem 7 tutorial](https://images-na.ssl-images-amazon.com/images/I/71NQzL1kwdL._AC_UL600_SR378,600_.jpg)
(1997) Physiological parameter values for physiologically based pharmacokinetic models. (1983) Interspecies pharmacokinetic scaling and the Dedrick plots. (1983) Evolutionary biology, animal behavior, fourth-dimensional space, and the raison d'etre of drug metabolism and pharmacokinetics. (1982) Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. (2011) Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models.
![nonmem 7 tutorial nonmem 7 tutorial](https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10928-020-09695-z/MediaObjects/10928_2020_9695_Fig3_HTML.png)
ICON Development Solutions, Maryland.īergstrand, M., Hooker, A. (2011) NONMEM User's guide, introduction to NONMEM 7.2.0. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.īauer, R. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. Recently, SMA has been extensively evaluated as an anti-cancer drug. 7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities.