Elimination pulmonary

Smallshaw JE, Ghetie V, Rizo J, Fulton JRJ, Trahan L, Ghetie MA, Vitetta E. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat Biotechnol 2003 21 387-91. 

No clinical treatments other than supportive measures are currently available to enhance elimination of trichloroethylene following exposure. Studies designed to assess the potential risks or benefits of increasing ventilation to enhance pulmonary elimination or of stimulating excretion of trichloroethylene and its decomposition products are needed. 

Pulmonary regulation ofPaC02, effectively allowing carbonic acid to be eliminated by the lungs as C02... 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

W. L. Chiou, Potential pitfalls in the conventional pharmacokinetic studies Effects of the initial mixing of drug in blood and the pulmonary first-pass elimination, J. Pharmacokinet. Biopharm., 7, 527-536 (1979). 

Bacterial products such as lipopolysaccharides (endotoxins) and cytokines (IL-2) are able to activate the contact system in vitro and in vivo (D9, H4, H7, M41). Immediately after severe trauma or after surgical intervention and particularly during sepsis, a reduction of plasma contact system proteins has been found (C10, K1, N9). Gel filtration studies of plasma demonstrated that plasma PK after activation becomes complexed with a2-M and Cl-Inh (W4). These complexes are rapidly eliminated from the circulation in vivo. In experimental studies in which pulmonary insufficiency was induced in dogs, a significant reduction of plasma kallikrein inhibitors was observed together with reduced HMK. Analysis of the relation be-... 

Once the oxygen has diffused from the alveoli into pulmonary circulation, it must be carried, or transported, in the blood to cells and tissues that need it. Furthermore, once the carbon dioxide has diffused from the tissues into the systemic circulation, it must be transported to the lungs, where it can be eliminated. This section considers mechanisms by which these gases are transported. 

Although absorption of fluorocarbons via inhalation is rapid, and maximal blood concentrations are reached in about 15 min, pulmonary uptake is low (Azar et al. 1973 Trochimowicz et al. 1974 Mullin et al. 1979). Negligible metabolism and tissue retention take place. Blood concentrations fall rapidly following cessation of exposure as the parent compound is exhaled unchanged. Rapid elimination is typical of poorly soluble materials with high vapor pressures and demonstrates a lack of potential to bioaccumulate (Emmen et al. 2000). 

The inhalation route for administering drugs into the pulmonary system for treatment of respiratory diseases eliminates many bioavailability problems such as plasma binding and first-pass metabolism, which are encountered in parenteral or oral administration. Consequently, a small inhalation dose is adequate for achieving... 

CNTs are of importance as useful bio-nanomaterials for pharmaceutical applications and biomedical engineering. However, despite the contribution of CNTs to bio-nanomaterials for pharmaceutical applications, the potential risks of CNTs about the exposure to human health have not been adequately assessed. Toxicology issues associated with CNT inhalation, dermal toxicity, pulmonary, biodistribution, biocompatibility, blood compatibility, and elimination need to be addressed prior to their pharmacological application in humans. 

In general, biotransformation reactions are beneficial in that they facilitate the elimination of xenobiotics from pulmonary tissues. Sometimes, however, the enzymes convert a harmless substance into a reactive form. For example, CYP-mediated oxidation often results in the generation of more reactive intermediates. Thus, many compounds that elicit toxic injury to the lung are not intrinsically pneumotoxic but cause damage to target cells following metabolic activation. A classic example of this is the activation of benzo(a)pyrene, which is a constituent of tobacco smoke and combustion products, and is... 

H. Foth, J. Hellkamp, E. M. Kunellis, G. E Kahl, Pulmonary Elimination and Metabolism of 5-Fluoro-2 -deoxyuridine in Isolated Perfused Rat Lung and Lung Slices , Drag Metab. Dispos. 1990, 18, 1011 - 1017. 

Excretion is the process of eliminating drugs from the body. They may be excreted as metabolites or as unchanged drug. As mentioned above, compounds that are polar and water soluble are more readily eliminated. The major routes of excretion are renal, biliary/fecal, lactational, and pulmonary. 

In humans. Fry et al. (1972) administered 500 mg of chloroform orally in olive oil in capsular form and found that 17-67% of the total dose of chloroform was exhaled as imchanged parent compound, and that the extent of pulmonary elimination of chloroform was governed inversely by the amount of adipose tissue on the individual ingesting the chloroform. The study also found that most of the chloroform tended to be exhaled between 40 minutes and 2 hours after dosing, which coincided with peak blood levels of chloroform produced at approximately 1 hour after dosing. 

The excretion of chloroform and its metabolites is understood, based on human and animal data derived from oral and inhalation studies (Brown et al. 1974a Corley et al. 1990 Fry et al. 1972 Taylor et al. 1974). The major route of chloroform elimination is pulmonary, but minor pathways are through enterohepatic circulation, urine, and feces as parent compound or metabolites. There are no human or animal data regarding excretion of dermally applied chloroform. 

One important mechanism of serotonin elimination is the (re-) uptake, e.g. by platelets. Furthermore, serotonin is metabolized by monoaminox-idase to 5-hydroxyindoleacetaldehyde and, subsequently, by an aldehyde dehydrogenase to 5-hydroxyindolacetic acid. The vascular effects of serotonin are complex. The direct interaction with vascular smooth muscle induces a vasoconstriction, whereas the stimulation of 5-HT-receptors on the endothelium induces the release of vasorelaxant factors with a dilatation as a result. An intravenous application of serotonin increases the pressure in the pulmonary circulation. A continuous infusion results... 

Lenalidomide, a derivative of thalidomide, was introduced in 2004. Patients with multiple myeloma stage II/III, who have undergone at least one previous treatment can be treated with bortezomib or with lenalidomide in combination with dexamethasone. There is good oral absorptin with peak plasma levels at 0.5-4 hours. Lenalidomide is maily eliminated by the kidneys with a half-life of circa 3-9 hours. Teratogenicity cannot be excluded. Side effects include thrombosis, pulmonary embolus, and hepato-toxicity, as well as bone marrow toxicity resulting in neutropenia and thrombocytopenia. 

---