To plasma

Pratt K J, Williams S K and Jarrell B E 1989 Enhanoed adherenoe of human adult andethelial sells to plasma disoharge modified polyethylene J. Blamed. Mater. Res. 23 1131-47... 

Chen F F 984 Introduction to Plasma Physics and Controlled Fusion (New York Plenum)... 

Mifepristone. After oral adininistration, peak plasma levels of mifepristone (84) (RU 486) are reached in 1 h and over 95% was bound to plasma proteins (351,352). The plasma half-life of RU 486 is approximately 24 h (352,353). In humans, monodemethylated (98), didemethylated (99) and alcohoHc nondemethylated (100) metaboHtes of RU 486 have been identified (351). These metaboHtes show some progestin-binding affinity, approximately five to ten times lower than that of RU 486 itself. RU 486 and its metaboHtes can be measured by radioimmunoassay and hplc (353,354). 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Diagnostic techniques that involve natural emissions are appHcable to plasmas of all sizes and temperatures and clearly do not perturb the plasma conditions. These are especially useful for the small, high temperature plasmas employed in inertial fusion energy research, but are also finding increased use in understanding the glow discharges so widely used commercially. 

Fig. 7. Schematic of a self-contained plasma processing unit designed to continuously plasma-treat and impregnate with resin, reinforcing fibers for enhanced composite strength. The unit can also be used to plasma-treat wires to be coated or treated for improved adhesion. Throughput speeds of over...

F. F. Chen, Introduction to Plasma Physics, Plenum Pubhshiag Corp., New York, 1974. 

Florfenicol has a wide tissue distribution, similar to that reported for chloramphenicol in calves and thiamphenicol in humans (43,44). Chloramphenicol attains concentrations higher than the corresponding plasma concentrations in bile and urine, as does florfenicol (43). Unlike florfenicol, chloramphenicol concentrations in the Hver, kidney, spleen, and lungs are less than corresponding plasma concentrations. However, chloramphenicol penetrates the brain and CSF much better than does florfenicol, reaching values equal to plasma concentrations in the brain. The distribution of thiamphenicol into the kidney, urine, and muscles of humans compared with corresponding plasma concentration is similar to what was observed for florfenicol in calves (44). The penetration of thiamphenicol into the CSF is much smaller than that of florfenicol in calves. 

Inorganic monomers can be used to plasma-deposit polymer-type films (16). At high plasma energies, the monomers are largely decomposed and can be used to form materials such as amorphous hydrogen-containing siUcon films from SiH for thin-film solar-ceU materials. 

The pursuit of further miniaturization of electronic circuits has made submicrometer resolution Hthography a cmcial element in future computer engineering. LB films have long been considered potential candidates for resist appHcations, because conventional spin-coated photoresist materials have large pinhole densities and variations of thickness. In contrast, LB films are two-dimensional, layered, crystalline soHds that provide high control of film thickness and are impermeable to plasma down to a thickness of 40 nm (46). The electron beam polymerization of CO-tricosenoic acid monolayers has been mentioned. Another monomeric amphiphile used in an attempt to develop electron-beam-resist materials is a-octadecylacryUc acid (8). 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

Disopyr mide. Disopyramide phosphate, a phenylacetamide analogue, is a racemic mixture. The dmg can be adininistered po or iv and is useful in the treatment of ventricular and supraventricular arrhythmias (1,2). After po administration, absorption is rapid and nearly complete (83%). Binding to plasma protein is concentration-dependent (35—95%), but at therapeutic concentrations of 2—4 lg/mL, about 50% is protein-bound. Peak plasma concentrations are achieved in 0.5—3 h. The dmg is metabolized in the fiver to a mono-AJ-dealkylated product that has antiarrhythmic activity. The elimination half-life of the dmg is 4—10 h. About 80% of the dose is excreted by the kidneys, 50% is unchanged and 50% as metabolites 15% is excreted into the bile (1,2). 

Phenytoin s absorption is slow and variable yet almost complete absorption eventually occurs after po dosing. More than 90% of the dmg is bound to plasma protein. Peak plasma concentrations are achieved in 1.5—3 h. Therapeutic plasma concentrations are 10—20 lg/mL but using fixed po doses, steady-state levels are achieved in 7—10 days. Phenytoin is metabolized in the fiver to inactive metabolites. The plasma half-life is approximately 22 h. Phenytoin is excreted primarily in the urine as inactive metabolites and <5% as unchanged dmg. It is also eliminated in the feces and in breast milk (1,2). Prolonged po use of phenytoin may result in hirsutism, gingival hyperplasia, and hypersensitivity reactions evidenced by skin rashes, blood dyscrasias, etc... 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

Elecainide is weU absorbed and 90% of the po dose is bioavailable. Binding to plasma protein is only 40% and peak plasma concentrations are attained in about 1—6 h. Three to five days may be requited to attain steady-state plasma concentrations when multiple doses are used. Therapeutic plasma concentrations are 0.2—1.0 lg/mL. Elecainide has an elimination half-life of 12—27 h, allowing twice a day dosing. The plasma half-life is increased in patients with renal failure or low cardiac outputs. About 70% of the flecainide in plasma is metabolized by the Hver to two principal metaboUtes. The antiarrhythmic potency of the meta-O-dealkylated metaboUte and the meta-O-dealkylated lactam, relative to that of flecainide is 50 and 10%, respectively. The plasma concentrations of the two metaboUtes relative to that of flecainide are 3—25%. Elecainide is mainly excreted by the kidneys, 30% unchanged, the rest as metaboUtes or conjugates about 5% is excreted in the feces (1,2). 

Acebutolol is well absorbed from the GI tract. It undergoes extensive hepatic first-pass metabohsm. BioavailabiUty of the parent compound is about 40%. The principal metaboflte, A/-acetylacebutolol, has antiarrhythmic activity and appears to be more cardioselective. Binding to plasma proteins is only 26%. Peak plasma concentrations of acebutolol are achieved in 2.5 h, 3.5 h for A/-acetylacebutolol. The elimination half-Hves of acebutolol and its metabohte are 3—4 and 8—13 h, respectively. The compounds are excreted by the kidneys (30—40%) and by the Hver into the bile (50—60%). About 40% of the amount excreted in the urine is unchanged acebutolol, the rest as metabofltes (32). 

Esmolol is iv adrninistered. Maximal P-adrenoceptor blockade occurs in 1 min. Its elimination half-life is about 9 min. EuU recovery from P-adrenoceptor blockade is within 30 min after stopping the infusion. The therapeutic plasma concentrations are 0.4—1.2 lg/mL. It is metabolized by hydrolysis in whole blood by red blood cell esterases resulting in the formation of a primary acid metabohte and free methanol. The metabohte is pharmacologically inactive. The resulting methanol levels are not toxic. Esmolol is 55% bound to plasma protein, the acid metabohte only 10%. Less than 2% of parent dmg and the acid metabohte are excreted by the kidneys. Plasma levels may be elevated and elimination half-hves prolonged in patients with renal disease (41). 

The GI absorption of the dmg after po adrninistration is slow and variable with estimates ranging from 20—55%. Once absorbed, 96% of the dmg is bound to plasma proteins and other tissues on the body. Whereas peak plasma concentrations may be achieved in 3—7 h, the onset of antiarrhythmic action may occur in 2—3 days or more. This may result, in part, from distribution to and concentration of the dmg in adipose tissue, Hver, spleen, and lungs. Therapeutic plasma concentrations are 1—2 p.g/mL, although there appears to be no correlation between plasma concentration and antiarrhythmic activity. The plasma half-life after discontinuation of the dmg varies from 13—103 days. The dmg is metabolized in the Hver and the principal metaboHte is desethylamiodarone. The primary route of elimination is through the bile. Less than 1% of the unchanged dmg is excreted in the urine. The dmg can also be eliminated in breast milk and through the skin (1,2). 

Sotalol is rapidly and almost completely (>90%) absorbed. Bioavahabhity of absorbed dmg is 89—100%. Peak plasma levels are achieved in 2—4 h. Sotalol is 50% bound to plasma proteins. Plasma half-life of the compound is about 5.2 h. No metabolites of sotalol have been identified indicating littie metabolism. The dmg is excreted mainly by the kidneys (80—90%) and about 10% is eliminated in the feces. The plasma half-life is prolonged in patients having renal failure. Kinetics of the compound are not affected by changes in liver function (1,2). Sotalol has ah the adverse effects of -adrenoceptor blockers including myocardial depression, bradycardia, transient hypotension, and proarrhythmic effects (1,2). 

After po dosing, verapamil s absorption is rapid and almost complete (>90%). There is extensive first-pass hepatic metabolism and only 10—35% of the po dose is bioavahable. About 90% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 1—2 h, although effects on AV nodal conduction may be apparent in 30 min (1—2 min after iv adrninistration). Therapeutic plasma concentrations are 0.125—0.400 p.g/mL. Verapamil is metabolized in the liver and 12 metabolites have been identified. The principal metabolite, norverapamil, has about 20% of the antiarrhythmic activity of verapamil (3). The plasma half-life after iv infusion is 2—5 h whereas after repeated po doses it is 4.5—12 h. In patients with liver disease the elimination half-life may be increased to 13 h. Approximately 50% of a po dose is excreted as metabolites in the urine in 24 h and 70% within five days. About 16% is excreted in the feces and about 3—4% is excreted as unchanged dmg (1,2). 

Moves towards anode and all electrons get absorbed there. The leftout neutrons come back to plasma uncharged... 

Papiz, M.Z., et al. The structure of p-lactoglobulin and its similarity to plasma retinol-binding protein. Nature 324 383-385, 1986. 

Water-soluble compounds are naturally easily transported in the blood. Non-soluble compounds are usually transported bound to plasma proteins (albumins). This binding is reversible in most cases but may vary remarkably. The degree of protein binding may vary between 50% and 99%. The proportion of the free (unbound) compound in the circulation is the amount of the compound that can reach the tissues and thus the target organs. Very lipid-... 

Steroid hormones act in a different manner from most hormones we have considered. In many cases, they do not bind to plasma membrane receptors, but rather pass easily across the plasma membrane. Steroids may bind directly to receptors in the nucleus or may bind to cytosolic steroid hormone receptors, which then enter the nucleus. In the nucleus, the hormone-receptor complex binds directly to specific nucleotide sequences in DNA, increasing transcription of DNA to RNA (Chapters 31 and 34). 

The recommended dose of pemetrexed is 500 mg/m2 administered as an intravenous infusion over 10 min on Day 1 of each 21-day cycle. Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70-90% of the dose recovered unchanged within the first 24 h following administration. Pemetrexed has a steady-state volume of distribution of 16.1 L. Pemetrexed is highly bound (approximately 81%) to plasma proteins. Binding is not affected by the degree of renal impairment. Plasma... 

Hydrophobic-tailed tetramers Abundant form in the mammalian CNS. Anchored to plasma membranes by a hydrophobic, 20 kDalton length polypeptide subunit named PRiMA (Proline-Rich Membrane Anchor). 

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