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Accumulation, of drugs

When pharmaceuticals are administered to feed animals there is a special concern about the possible accumulation of drug residues in the animals tissues. Thus, in these bioequivalency studies it may be appropriate to carefully monitor parameters that define possible tissue accumulation [45]. [Pg.757]

Fromm, M. F. P-glycoprotein a defense mechanism limiting oral bioavailability and CNS accumulation of drugs, frit. J. Clin. Pharmacol. Ther. 2000, 38, 69-74. [Pg.287]

This can be further simplified if it is assumed that there is no accumulation of drug on the blood side (i.e. < < CJ ) or the portal blood is considered... [Pg.42]

Madden ThD, Harrigan PR, et al. The accumulation of drugs within large unilamellar vesicles exhihibiting a proton gradient a survey. Chem Phys Lipids 1990 53 37-46. [Pg.23]

ABCG2 Topotecan Increased accumulation of drug in cells (94) Increased bioavailability in (94)... [Pg.56]

High accumulation of drug in tissues has also been implicated in the seven-fold longer elimination half-life of the dibasic antiarrhythmic, disobutamide (Figure 4.11) compared to the monobasic agent, disopyramide. The elimination half-life of disobutamide is 54 h compared to approximately 7 h for disopyramide. [Pg.56]

Aerosol Use of aerosolized ribavirin in patients requiring mechanical ventilator assistance should be undertaken only by health care providers and support staff familiar with the specific ventilator being used and this mode of administration of the drug. Pay strict attention to procedures that have been shown to minimize the accumulation of drug precipitate that can result in mechanical ventilator dysfunction and associated increased pulmonary pressures. [Pg.1771]

Accumulation of drug or metabolites in red blood cells occurs, with plateauing in red cells in about 4 days. Accumulation gradually declines with an apparent half-life of 40 days. [Pg.1777]

Resistance is related largely to changes in cell permeability and a resultant decreased accumulation of drug due to increased efflux from the cell by an energy-dependent mechanism. Other mechanisms, such as production of a protein that alters the interaction of tetracycline with the ribosome and enzymatic inactivation of the drug, have been reported. [Pg.544]

Other drug reservoirs are cellular and fat reservoir. The accumulation of drug in the cells may be the result of active transport or binding. Many drugs are accumulated in muscle and other cells in higher concentration than in the extracellular fluids. Many lipid soluble drugs are stored in the neutral fat, and act as the important reservoir. [Pg.30]

Dosage adjustments must be made to prevent accumulation of drug and toxicity in patients with renal insufficiency. Either the dose of drug is kept constant and the interval between doses is increased, or the interval is kept constant and the dose is reduced. Nomograms and formulas have been constructed relating serum creatinine levels to adjustments in... [Pg.1022]

When lasalocid was fed to layer hens at a dosage of 5 ppm, considerable accumulation of drug residues in eggs occurred (25) the highest mean egg lasalocid concentration in eggs was found to be in excess of 400 ppb after the medication period. [Pg.167]

The distribution of drugs depends on both the physicochemical properties of the drug molecules and the composition of tissue membranes. These factors can either result in a uniform or uneven distribution of dmgs into the various body compartments and fluids. In the extreme, distribution may tend toward an accumulation of drugs in particular tissues or to an almost complete exclusion of the drag from a particular compartment in a defined length of time. One unique compartment that has to be considered in this respect is the brain, which is separated from the capillary system of the blood by the blood-brain barrier, whose membrane has a special structure. It consists of a cerebral capillary network formed by a capillary endothelium that consists of a cell layer with continuous compact intercellular junctions. It has no pores, but special cells, astrocytes, which support the stability of the tissues, are situated at the bases of the endothelial membrane separating the brain and CSF from the blood. The astrocytes form an envelope around the capillaries. [Pg.168]

Under in vivo conditions, not only the degree of partitioning but also the dissociation constant of the lipid-drug complex is of importance. It is evident that the accumulation of drug molecules in the various cell membranes can have an enormous influence on the pharmacokinetics of drugs and, in consequence, on effectivity, selectivity, and toxicity. [Pg.199]

To study the possible effect of membrane biophysical properties on drug accumulation, the lipid composition of membranes has deliberately been altered by growing cells in the presence of anionic phospholipids, saturated or unsaturated fatty acids, or other components affecting membrane properties, e.g. cholesterol [102, 103]. The accumulation of drugs in MDR hamster cell lines (CHRC5) was increased when membrane properties were altered. For this purpose the cells were cultured in a medium supplemented with C17 0 fatty acid. The cells showed an extent of vinblastine accumulation similar to that found in the sensitive wild-type counterparts (AB1) (Figure 5.15) [103]. [Pg.253]


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