Half-life in plasma

When levels of conjugated bilirubin remain high in plasma, a fraction can bind covalently to albumin (delta bilirubin). Because it is bound covalently to albumin, this fraction has a longer half-life in plasma than does conventional conjugated bilirubin. Thus, it remains elevated during the recovery phase of obstructive jaundice after the remainder of the conjugated bilirubin has declined to normal levels this explains why some patients continue to appear jaundiced after conjugated bilirubin levels have returned to normal. 

Many of the coagulation factors measured by global coagulation tests have limited stability, and the time and temperature of storage of sample will affect their measurements. Concepts of analyte stability and half-life in plasma extend to markers measured by immunoassay. Markers of platelet activation are affected by artifactual activation in vitro upon collection of the blood specimen. This section will highlight some of the nonanalytical variables that, if uncontrolled, can lead to spurious results and thus affect the interpretation of laboratory data. 

The biological half-life in plasma of Lp(a) equals that of LDL (K37). However, LDL-receptor activity does not fully account for the main catabolic pathway of Lp(a) (A13, A15, K19, Ml, M10). Only a modest uptake, if any, of Lp(a) by the LDL receptors has been reported (F12, H21, K37, S36). Moreover, this uptake can possibly be influenced by the presence of other apolipoproteins as apo-E (B4, H37, K20). 

Artemisinin (18) is a natural product for which many semisynthetic derivatives have been generated. The major rationale to produce these derivatives was to deal with the low aqueous solubility of artemisinin and its short half-life in plasma. The lipid-soluble arteether (22) and artemether (23), and the water-soluble sodium artesunate (24), were designed for... 

Excretion - The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose was recovered in the feces, which consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1 % to 2% of the dose was recovered in the urine, of which unchanged nelfinavir was the major component. 

Paracetamol, synonym acetaminophen, is world wide probably the most popular analgesic and antipyretic. Its mechanism of action is not well understood. It is not really an NSAID as it is only a very weak inhibitor of cyclo-oxygenase and has hardly any anti-inflammatory activity. For the same reason paracetamol gives only negligible gastrointestinal irritation and gives hardly any blockade of platelet aggregation. Paracetamol concentrations in plasma reach a peak in 30-60 minutes, and the half-life in plasma is about 2 hours. Almost 100% of... 

Prazosin is readily absorbed after oral administration, peak serum levels occur approximately 2 hours after a single oral dose, and the antihypertensive effect of prazosin persists for up to 10 hours. Its half-life in plasma ranges from 2.5 to 4 hours, and elimination from plasma appears to follow first-order kinetics. The drug is extensively (perhaps as high as 97%) bound to plasma proteins this observation partially explains the lack of correlation between plasma drug levels and persistence of antihypertensive effect. 

Cytarabine is rapidly metabolized in the liver, kidney, intestinal mucosa, and red blood cells and has a half-life in plasma of only 10 minutes after intravenous bolus injection. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of a given dose is excreted in the urine within 24 hours, with less than 10% appearing as cytarabine the remainder is ara-U. When the drug is given by continuous infusion, cytarabine levels in CSF approach 40% of those in plasma. 

Warfarin is generally administered as the sodium salt and has 100% bioavailability. Over 99% of racemic warfarin is bound to plasma albumin, which may contribute to its small volume of distribution (the albumin space), its long half-life in plasma (36 hours), and the lack of urinary excretion of unchanged drug. Warfarin used clinically is a racemic mixture composed of equal amounts of two enantiomorphs. The levorotatory S-warfarin is four times more potent than the dextrorotatory R-warfarin. This observation is useful in understanding the stereoselective nature of several drug interactions involving warfarin. 

Glucagon is extensively degraded in the liver and kidney as well as in plasma and at its tissue receptor sites. Because of its rapid inactivation by plasma, chilling of the collecting tubes and addition of inhibitors of proteolytic enzymes are necessary when samples of blood are collected for immunoassay of circulating glucagon. Its half-life in plasma is between 3 and 6 minutes, which is similar to that of insulin. 

Following parenteral administration to laboratory animals, the elimination half-life in plasma was 0.8-1.5 h, with the highest tissue concentrations appearing in kidney and liver. Mecillinam was excreted mainly through the urine within the first few hours after administration. Seven metabolites were found in dog urine, but only the formyl-6-aminopenicillanic acid could be identified. 

Pharmacokinetic studies in pigs following a single oral administration of 20 mg kitasamycin/kg bw showed that the drug was rapidly absorbed and distributed in the body. A maximum plasma concentration of 4.5 ppm was attained within 0.5 h, the half-life in plasma being 0.7 h. Highest tissue residue concentrations (21 ppm) were detected in kidney within 1-2 h. The ratio of the maximum concentrations determined in kidney to that in liver was around 3 2. 

In another experiment with rainbow trout given oral trimethoprim at different dosage levels, the elimination half-life in plasma was found to be approxi-... 

All these studies suggest that the metabolic pathway is the same for free and bound forms of ferulic acid. Whereas the free form is rapidly absorbed, metabolized and excreted in urine, the bound form allows a longer time period (free and conjugated) in plasma, as already suggested by the absence of free ferulic acid in rat plasma 18 h after intake from an enriched diet, whereas its metabolites were still present [Adam et al., 2002]. Even though its bioavailability, in terms of half-life in plasma and low excretion in urine, was improved when esterified, the absorption of ferulic acid from a wheat source was lower than if present as free form in a diet [Rondini et al., 2004]. This indicates that the amounts of ferulic acid circulating in plasma as well as its circulating metabolites are dependent on its form present in the food source. 

A biological half-life in whole blood of 386 hours and a biological half-life in plasma of 271 hours have been reported(32) Detectable levels of reserpine may be found after 11 days from administration of the drug. Reserpine is not removed either by hemodialysis or by peritoneal dialysis(36). 

The choice of the concentration of the drug to be tested should consider therapeutic levels that could be attained with clinically employed doses. In the case of a compound under pre-clinical evaluation for a potential antitumor activity, a concentration limit of 100 pg/ml is recommended. Pharmacokinetic data are available for various anti-neoplastic clinically used drugs, with information about their maximum plasma concentration, concentration versus time, and pharmaceutical half-life in plasma. When these data are not available, an approximation of plasma levels could be obtained by calculating the theoretical concentration obtained when the administered dose is uniformly distributed throughout the body fluid. 

Further studies have validated this hypothesis, in part,4 and ultimately this inventive premise was borne out in clinical practice. As a result, 5-FU (5) was eventually approved for treatment of solid tumors, such as breast, colorectal, and gastric cancers. Marketed as Adrucil when administered intravenously, 5-FU can be used either as monotherapy or combination therapy with various cytotoxic drugs and biochemical modulators, such as leucovorin and methotrexate.5 Because 5-fluorouracil is not orally bioavailable, it must be administered by continuous infusion to optimize its efficacy due to its short half-life in plasma. In addition, 5-FU has poor selectivity toward tumors in vivo, and its distribution into tissues such as bone marrow, the gastrointestinal tract, the liver and skin causes high incidences of toxicity. In addition, in spite of its limited lipid solubility, 5-fluorouracil diffuses readily across the blood-brain barrier into cerebrospinal fluid and brain tissue.1,5... 

Short Half-Life in Plasma and Long Half-Life for Enzyme-Inhibitor Complex... 

Triamcinolone is reported to have a half-life in plasma of about 2 h to over 5 h. It is bound to plasma albumin to a much smaller extent than hydrocortisone. The acetonide, diacetate, and hexacetonide esters of triamcinolone are only very slowly absorbed from injection sites. 

Naproxen is a propionic acid derivative that has a structure similar to ibuprofen and ketoprofen. It can be administered either i.v. or p.o. to horses, even though it is poorly absorbed with a bioavailability of approximately 50% (Pasargiklian Bianco 1986). It has a relatively short half-life in plasma (4h) (Tobin 1979). There is little information available on the therapeutic index of naproxen in the horse. 

The incorporation of vinyl groups into antibacterial Cl 2 ketolides has a favorable impact on the pharmacokinetic and pharmacodynamic properties increase of the lung to plasma AUC ratio, of the bioavailability, and half-life in plasma and lung. These properties directly impact on the in vivo potent efficacy in rat lung infection models." ... 

When the apparent half-life of the drug candidate or a metabolite in organs or tissues significantly exceeds the apparent terminal disposition half-life in plasma and is more than twice the dosing interval in toxicity studies... 

PretreatmentSleeping time (min) Plasma level of pentobarbital on Pentobarbital half-life in plasma... 

Studies in animals have recently been ex-taided to humans. ISIS 104838, a TNFa anti-sense inhibitor, a 2 -0-(2-methoxyethyl) chimera, was shown to reduce TNF a secretion at doses at least 10 times lower than would be expected in humans by first-generation anti-saise drugs (Dorr, unpublished observations, 2001) and to have an elimination half-life in plasma of approximately 30 days (Geary, unpublished observations, 2001). These studies demonstrate the feasibility of once-a-month dosing. 

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