Tissue sequestration

Like most quaternary ammonium compounds, 2-PAM is distributed mainly to extracellular water, and some tissue sequestration occurs.100 2-PAM is only weakly bound to plasma proteins.100... 

Another model, which is increasingly being used, is the physiologically based pharmacokinetic model. This uses data on the absorption, distribution, metabolism, tissue sequestration, kinetics, elimination, and mechanism to determine the target dose used for the extrapolation, but it requires extensive data. 

Human birth defects have also been observed after prenatal exposure to etretinate. Of particular significance in the case of this drug is that measurable serum concentrations have been documented more than 2 years after cessation of therapy, suggesting a remarkable example of tissue sequestration. Therefore, the risk of teratogenicity may exist for an extended period of time. 

Percutaneous drainage may be limited by antelocated intestinal loops or by abscesses that are difficult to reach. Similarly, surgery is indicated following unsuccessful percutaneous drainage, in extensive cavernous or multifocal abscesses, tissue sequestration, formation of enteral fistula and viscous abscess contents as well as local recurrences. With abscess perforation or the existence of other purulent foci in the abdomen, surgical intervention is called for immediately. 

In the later serum-gentamicin determinations, the elevation of measured serum-drug concentration over levels predicted by the pharmacokinetic model is most likely due to the inability of a one-compartment distribution model to properly describe the observed tissue sequestration of gentamicin and the later return of the drug from the tissues to the vascular compartment. This process would delay total drug excretion and cause an elevation of the later-time measurements of serum gentamicin concentration. 

Amiodarone has an extremely long half-life—up to 103 days. It may be as long as several weeks before the effects of the drug decrease after the drug is withdrawn, due to the long half-life and tissue sequestration. 

Azithromycin undergoes some hepatic metabolism to inactive metabohtes, but biliary excretion is the major route of ehmination. Only 12% of drug is excreted unchanged in the urine. The tj, 40-68 hours, is prolonged because of extensive tissue sequestration and binding. 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

This experimental drug is a derivative of myriocin. After phosphorylation FTY720 modulates chemotactic responses and lymphocyte trafficking, leading to reversible lymphocyte sequestration in secondary lymphoid tissues. It is in clinical trials for the treatment of multiple sclerosis. 

Metallothioneins are a group of small proteins (about 6.5 kDa), found in the cytosol of cells, particularly of liver, kidney, and intestine. They have a high content of cysteine and can bind copper, zinc, cadmium, and mercury. The SH groups of cysteine are involved in binding the metals. Acute intake (eg, by injection) of copper and of certain other metals increases the amount (induction) of these proteins in tissues, as does administration of certain hormones or cytokines. These proteins may function to store the above metals in a nontoxic form and are involved in their overall metaboHsm in the body. Sequestration of copper also diminishes the amount of this metal available to generate free radicals. 

One of the most notable features of this inherited defect of iron homeostasis (Chapter 9) is the ability of individuals to accumulate large amounts of iron over many years and yet show no apparent adverse effects. This may in part be due to the ability of tissues, notably the liver, to increase their iron stores gradually over a long period of time, successfully sequestrating excess iron into ferritin and, predominantly, haemosiderin. However with time the excessive deposition of iron will cause a variety of toxic effects including diabetes and arthritis which are caused by deposition of iron in these tissues. Removal of this iron by venesection can often reduce these iron-induced symptoms. 

The activity of G protein Py subunits is modulated by another protein termed phosducin [16]. Phosducin is a cytosolic protein enriched in retina and pineal gland but also expressed in brain and other tissues. Phosducin binds to G protein Py subunits with high affinity. The result is prevention of Py subunit reassociation with the a subunit. In this way, phosducin may sequester Py subunits, which initially may prolong the biological activity of the a subunit. However, eventually this sequestration may inhibit G protein activity by preventing the direct biological... 

Endothelial permeability Transporter proteins Enzymatic/metabolic activity Disease Tissue composition (drug sequestration) Dose size/volume Conformation Chemical stability Enzymatic stability... 

Pentamidine is not well absorbed from the intestinal tract after oral administration and generally is given by intramuscular injection. The drug binds to tissues, particularly the kidney, and is slowly excreted, mostly as the unmodified drug. It does not enter the central nervous system (CNS). Its sequestration in tissues accounts for its prophylactic use in trypanosomiasis. 

N.R. Bolo, Y. Mode, J.P. Macher, Long-term sequestration of fluorinated compounds in tissues after fluvoxamine or fluoxetine treatment A fluorine magnetic resonance spectroscopy study in vivo, MAGMA 16 (2004) 268-276. 

---