Bioavailability plasma

Keywords ADME-Tox solubility Caco-2 absorption blood-brain barrier human intestinal absorption oral bioavailability plasma protein binding QSAR... 

Drug Oral Bioavailability (%) Plasma Elimination Half-Life (hr) Protein Binding (%) Metabolism Urinary Excretion" (%) Notes... 

The focus before IND is on Tmax, Cmax and AUCs, while the complexity of pharmacokinetic characterization (like oral bioavailability, plasma half life, volume of distribution, mean residence time, absorption, solubility and concentration) is built up during clinical trials and on the basis of comparable human data. 

ABSORPTION AND ELIMINATION The oral bioavailability, plasma tj, and route of elimination of the available osmotic diuretics are listed in Table 28-3. Glycerin and isosorbide can be given orally mannitol and urea must be administered intravenously. 

ABSORPTION AND ELIMINATION The oral bioavailabilities, plasma tj, and routes of elimination of inhibitors of Na+-K+-2CL symport are listed in Table 28. Because these drugs are bound extensively to plasma proteins, their delivery to the tubules by filtration is limited. However, they are secreted efficiently by the organic acid transport system in the proximal tubule and thereby gain access to their binding sites on the Na+-K+-2Q" symporter in the luminal membrane of the TAL. 

Cidofovir has very low oral bioavailability. Plasma levels after intravenous dosing decline bipha-sically with a terminal t of 2.6 hours. The volume of distribution approximates total-body water. CSFpenetration is low. Topical cidofovir gel may result in low plasma concentrations (<0.5 pg/mL) in patients with large mucocutaneous lesions. 

Key PK parameters such as bioavailability, plasma elimination half-life, clearance, and volume of... 

Despite low apparent bioavailability, plasma concentrations of anthocyanins appear sufficient to induce changes in signal transduction and gene expression in vivo [67, 68] in a manner that suggests their putative role in physiological functions and health outcomes. 

Carotenoid isomerization can occur in the acidic gastric milieu. Lycopene present in fruits and vegetables occurs almost exclusively as the aW-trans isomer, but is converted to cis isomers, which seem to be more bioavailable. Plasma and tissue profiles show that cis isomers make up more than 50% of the total lycopene present. On the other hand, studies show that no trans/cis isomerization of /3-carotene occurs in the stomach. In fact, evidence has been found for transfer of a significant portion of both /3- and a-carotene to the fat phase of the meal in the stomach, which would increase bioavailability of these carotenoids for absorption. No studies are available relating isomerization to bioavailability of other carotenoids. 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

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). 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

Bopindolol is a long-acting, nonselective P-adrenoceptor blocker. It has mild membrane stabilizing activity and ISA. In vivo, the compound is hydrolyzed to its active metabohte. Because of this prodmg feature the onset of action is slower than other available P-adrenoceptor blockers. Preliminary pharmacokinetic studies indicate that the compound is weU absorbed, is 70% bioavailable, and peak plasma levels are achieved in about 2 h. Whereas its elimination half-life is 4—8 h, P-adrenoceptor blocking action (- 40%) is stiU apparent after 48 h. The dmg is being studied in hypertension, angina, and arrhythmias (43). 

Nicardipine is almost completely absorbed after po adrninistration. Administration of food decreases absorption. It undergoes extensive first-pass metaboHsm in the Hver. Systemic availabiHty is dose-dependent because of saturation of hepatic metaboHc pathways. A 30 mg dose is - 35% bioavailable. Nicardipine is highly protein bound (>95%). Peak plasma concentrations are achieved in 0.5—2.0 h. The principal path of elimination is by hepatic metaboHsm by hydrolysis and oxidation. The metaboHtes are relatively inactive and exert no pharmacological activity. The elimination half-life is 8.6 h. About 60% of the dose is excreted in the urine as metaboHtes (<1% as intact dmg) and 35% as metaboHtes in the feces (1,2,98,99). 

The absorption of metoprolol after po dosing is rapid and complete. The dmg undergoes extensive first-pass metabolism in the liver and only 50% of the po dose in bioavailable. About 12% of the plasma concentration is bound to albumin. The elimination half-life is 3—7 h and less than 5% of the po dose is excreted unchanged in the urine. The excretion of the dmg does not appear to be altered in patients having renal disease (98,99,108). 

Eventually, the proposed method was successfully applied to quantify clarithromycin in spiked human plasma and real samples from healthy volunteers after oral administration of the dmg indicating the utility of this method for clinical and bioavailability studies. 

The pharmacokinetics of azacitidine shows that it is rapidly absorbed after s.c. administration with the peak plasma concentration occurring after 0.5 h. The bioavailability of s.c. azacitidine relative to i.v. azacitidine is approximately 89%. Urinary excretion is the primary route of elimination of azacitidine and its metabolites. The mean elimination half-lives are about 4 h, regardless of i.v. or s.c. administration. 

Area under the Curve (AUC) refers to the area under the curve in a plasma concentration-time curve. It is directly proportional to the amount of drug which has appeared in the blood ( central compartment ), irrespective of the route of administration and the rate at which the drug enters. The bioavailability of an orally administered drug can be determined by comparing the AUCs following oral and intravenous administration. 

Bioavailability is the amount of drug in a formulation that is released and becomes available for absorption or the amount of the drug absorbed after oral administration compared to the amount absorbed after intravenous administration (bioavailability - 100%), judged from areas remaining under plasma drug concentration-time curves. 

Diclofenac is an exceedingly potent COX inhibitor slightly more efficacious against COX-2 than COX-1. Its absorption from the gastrointestinal tract varies according to the type of pharmaceutical formulation used. The oral bioavailability is only 30-80% due to a first-pass effect. Diclofenac is rapidly metabolised (hydroxylation and conjugation) and has a plasma half-life of 1.5 h. The metabolites are excreted renally and via the bile. 

VAN HET HOF K H, DE BOER B C, TIJBURG L B, LUCIUS B R, ZIJP I, WEST C E, HAUTVAST J G and WESTRATE J A (2000) Carotenoid bioavailability in humans from tomatoes processed in different ways determined from the carotenoid response in the triglyceride-rich lipoprotein fraction of plasma after a single consumption and in plasma after 4 days of consumption. JNutr 130(5) 1189-96. 

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