Erythrocytes half-life

Based on this experience, all gouty patients with suspected purine overproduction not due to hereditary enzyme abnormalities were evaluated for the presence of compensated hemolysis. So far, 7 patients have been found in which the serum haptoglobin level was indicative of hemolysis (Table 5). In 5 of these patients, a shortened erythrocyte half-life was also found. 

These small-molecule thiols serve to transfer NO from erythrocytes to endothelial receptors, where it acts to relax vascular tension. NO itself is a reactive free-radical compound whose biological half-life is very short (1-5 sec). S-nitrosoglutathione has a half-life of several hours. 

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

PbB concentrations reflect the absorbed dose of lead. However, the interpretation of PbB data depends on a knowledge of the past history of exposure to lead. This is because in the body, bone constitutes the major lead sink and this results in lead having a long body half-life. Thus, in the absence of intense exposure to lead for a considerable period up to its body half-life, the PbB concentrations reflect recent lead exposures. However, if intermittent exposure to lead is occurring in several distinct environments, the PbB concentration reflects both recent and past exposures to lead. Thus, biological effects for populations with the same PbB concentrations may not be the same since different exposure times scales may be involved. This is the reason why free erythrocyte protoporphyrin (FEP) and erythrocyte zinc protoporphyrin (ZPP) have been used as additional biological markers since their elevation is more related to chronic lead exposure than acute lead exposure (see Section 2.7). 

From the comparison by Nyman et al. between plasma Hp level and different red cell destruction indices (half-life of CrB1-tagged erythrocytes, endogenous CO formation, stercobilin (urobilin) excretion in feces) it is evident that anhaptoglobinemia is a very common, but not an invariable accompaniment of increased red cell turnover. The exceptions are possibly persons with increased Hp synthesis. Individual differences in efficiency to destroy red cells outside the circulation without Hb return may be reflected by the wide normal variation range of plasma Hp as well by the promptness with which anhaptoglobinemia develops on even slight increase in Hb turnover. 

Hp calculated by Nyman as 5 days may represent the half-life as a result of the normal catabolism—type (a)—if we ignore the erythrocyte destruction. It is meaningless to speak of half-life values of Hp when discussing Hp turnover absolute amount per unit of time and weight should, instead, be used. 

The plasma protein binding of tacrolimus is approximately 99%. Tacrolimus is bound mainly to albumin and alpha-1-acid glycoprotein and has a high level of association with erythrocytes. It is extensively metabolized by the mixed-function oxidase system, primarily the cytochrome P450 system (CYP3A). The disposition of tacrolimus from whole blood was biphasic with a terminal elimination half-life of 11.7 hours in liver transplant patients. 

Ethambutol is a synthetic agent and not related to any of the other tuberculostatics. Its mechanism of action is not well understood but in actively dividing mycobacteria it appears to be an inhibitor of mycobacterial RNA synthesis. It also has effects on bacterial phosphate metabolism and on polyamine synthesis. It is an bacteriostatic agent and its main function in combination therapy is to delay the occurrence of resistance, mainly against isoniazid and rifampicin. It is well absorbed after oral administration. It is widely distributed, except to the CNS. Protein binding is about 20-30%. It is mainly excreted unchanged in the bile and urine with an elimination half-life of 3 h. Ethambutol is concentrated in erythrocytes and thus provides a depot for continuous release. 

Ribavirin is reversibly phosphorylated by all nucleated cells. It is also metabolized in the liver to a triazole carboxylic acid metabolite that is eliminated in the urine along with the parent compound. The plasma half-life of ribavirin is 9.5 hours when it is administered by aerosol (2.5 hours/day for 3 days), whereas its half-life is around 12.5 days at steady state. The drug accumulates in erythrocytes, with a half-life of 40 days. 

Azathioprine is well absorbed following oral administration, with peak blood levels occurring within 1 to 2 hours. It is rapidly and extensively metabolized to 6-mercaptopurine, which is further converted in the liver and erythrocytes to a variety of metabolites, including 6-thiouric acid. Metabolites are excreted in the urine. The half-life of azathioprine and its metabolites in the blood is about 5 hours. 

Pharmacokinetics Rapidly, completely absorbed from G1 tract rectal absorption variable. Widely distributed to most body tissues. Acetaminophen is metabolized in liver excreted in urine. Dichloralphenazone is hydrolyzed to active compounds chloral hydrate and antipyrine. Chloral hydrate is metabolized in the liver and erythrocytes to the active metabolite trichloroethanol, which maybe further metabolized to inactive metabolite. It is also metabolized in the liver and kidneys to inactive metabolites. The pharmacokinetics of isometheptene is not reported. Removed by hemodialysis. Half-life Acetaminophen 1-4 hr (half-life is increased in those with liver disease, elderly, neonates decreased in children). 

Pharmacokinetics Rapidly absorbed. Protein binding 95%. Widely distributed throughout body tissues including erythrocytes, kidneys, and blood-brain barrier. Not metabolized. Excreted unchanged in urine. Removed by hemodialysis. Half-life 2.4-5.8 hr. 

Reacts with Flgb in erythrocytes, producing cyanmethemoglobin, and cyanide ions. Primarily excreted in urine. Half-life less than 10 min. 

Pharmacokinetics Rapidly and extensively absorbed after PO administration. Proteinbinding 50%. Widely distributed, includingtoCSFand erythrocytes. Metabolized in the liverto inactive metabolites. Primarily excreted in urine. Unknown if removed by hemodialysis. Half-life 1.5 hr. 

The pharmacokinetics of topiramate are linear with peak plasma concentrations (occurring in about 2 hours) of 25 pM after 400 mg daily (Shank et al., 2000). Topiramate is poorly bound to plasma proteins (15%) and it binds to erythrocytes. In rats the maximal concentration in the brain when administered at 10 mg/kg was 10 pM (Shank et ah, 2000). It is not extensively metabolized in humans and is eliminated (70%) unchanged in urine. Six minor metabolites have been identified, none with anticonvulsant activity. The average elimination half-life is 21 hours (Shank et ah, 2000). 

While it is assumed that hematopoietic cell formation is regulated through a concerted and coordinated release of factors in a cascade and series of reactions, the details of how such processes occur remain elusive. It is clear, however, that there are important differences in the growth and turnover (or removal) rates of blood cells. A new population of neutrophils is generated every 24 hours to replace aging cells, which are cleared with a half-life of about 6 to 8 hours [7]. On the other hand, erythrocytes exhibit a well-documented life... 

The first evidence that supplementation of exogenous ADA may be helpful in SCID patients came from the 1975 report of Potmar et al. [8], demonstrating that addition of bovine-intestinal ADA or human-erythrocyte ADA to cultures of lymphocytes of a SCID patient restored their ability to proliferate when stimulated with mitogens. The ability to respond to mitogens is an indicator of immune function restoration. Therapeutic use of enzyme extracted from calf tissue revealed that this form of ADA has a short half-life. 

Halofantrine hydrochloride, a phenanthrene-methanol, is effective against erythrocytic (but not other) stages of all four human malaria species. Oral absorption is variable and is enhanced with food. Because of toxicity concerns, it should not be taken with meals. Plasma levels peak 16 hours after dosing, and the half-life is about 4 days. Excretion is mainly in the feces. The mechanism of action of halofantrine is unknown. The drug is not available in the USA (although it has been approved by the FDA), but it is widely available in malaria-endemic countries. 

Adalimumab is a completely human IgGi approved for use in rheumatoid arthritis. Like the other anti-TNF- biologicals, adalimumab blocks the interaction of TNF- with TNF receptors on cell surfaces it does not bind TNF-3. Pharmacodynamic studies showed that administration of adalimumab reduced levels of C-reactive protein, erythrocyte sedimentation rate, serum IL-6, and matrix metalloproteinases MMP-1 and MMP-3. In vitro, adalimumab lyses cells expressing TNF- in the presence of complement. Patients may self-administer single doses of the antibody subcutaneously, every other week. Adalimumab has a serum half-life of 2 weeks, which is increased by 29-44% in patients who are also taking methotrexate. 

After absorption, lead enters the blood, and 97% is taken up by red blood cells. Here, lead has a half-life of two to three weeks during which there is some redistribution to the liver and kidney, then excretion into bile or deposition in bone. After an initial, reversible, uptake into bone, lead in bone becomes incorporated into the hydroxyapatite crystalline structure. Because of this, past exposure to lead is possible to quantitate using X-ray analysis. It is also possible to detect lead exposure and possible poisoning from urine and blood analysis, and the amount in blood represents current exposure. However, as lead is taken up into the red blood cell, both the free blood lead level and that in the erythrocytes needs to be known. 

In premature infants, whose reserves of the vitamin are inadequate, vitamin E deficiency causes a shortened half-life of erythrocytes, which can progress to increased intravascular hemolysis, and hence hemolytic anemia. In infants treated with hyperbaric oxygen, there is a risk of damage to the retina (retro-lental fibroplasia), and vitamin E supplements may be protective, although this is not firmly established (Phelps, 1987). 

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