Compartment multiple peripheral

As gene carriers are internalized by endocytosis, the motion characteristics inside the cell resembles the movement of the endosomal compartments within the cell and the formed vesicles are transported along the microtubule network [38]. Suh et al. [41] quantified the transport of individual internalized polyplexes by multiple-particle tracking and showed that the intracellular transport characteristics of polyplexes depend on spatial location and time posttransfection. Within 30 min, polyplexes accumulated around the nucleus. An average of the transport modes over a 22.5 h period after transfection showed that the largest fraction of polyplexes with active transport was found in the peripheral region of the cells whereas polyplexes close to the nucleus were largely diffusive and subdiffusive. Disruption of the microtubule network by nocodazole completely inhibits active transport and also the perinuclear accumulation of polyplexes [37, 40, 47]. 

The one-compartment model of distribution assumes that an administered drug is homogeneously distributed throughout the tissue fluids of the body. For instance, ethyl alcohol distributes uniformly throughout the body, and therefore any body fluid may be used to assess its concentration. The two-compartment model of distribution involves two or multiple central or peripheral compartments. The central compartment includes the blood and extracellular fluid volumes of the highly perfused organs (i.e., the brain, heart, liver, and kidney, which receive three fourths of the cardiac output) the peripheral compartment consists of relatively less perfused tissues such as muscle, skin, and fat deposits. When distributive equilibrium has occurred completely, the concentration of drug in the body will be uniform. 

Last, population pharmacokinetics of sibrotuzumab, a humanized monoclonal antibody directed against fibroblast activation protein (FAP), which is expressed in the stromal fibroblasts in >90% of malignant epithelial tumors, were analzyed in patients with advanced or metastatic carcinoma after multiple IV infusions of doses ranging from 5 mg/m to a maximum of 100 mg (78). The PK model consisted of two distribution compartments with parallel first-order and Michaelis-Menten elimination pathways from the central compartment. Body weight was significantly correlated with both central and peripheral distribution volumes, the first-order elimination clearance, and ymax of the Michaelis-Menten pathway. Of interest was the observation that body surface area was inferior to body weight as a covariate in explaining interpatient variability. 

---