Metabolism protein binding

Pharmacokinetics Unknown absorption, distribution, metabolism. Protein binding 50%-80%. Elxcreted in urine. Half-life 10-20 hr. 

Terbinqfine is a synthetic allylamine that is structurally similar to naftifine. It probably acts by inhibiting fungal squalene epoxidase and blocking ergosterol biosynthesis. Terbinafine is well absorbed, but bioavailability is only 40% because of first-pass hepatic metabolism. Proteins bind... 

Chose on basis of patient s background [former response to drugs, age, gender, concomitant physical disorders, concomitant drugs (hepatic metabolism, protein-binding capacity, synergistic adverse effects) and physician s experience]... 

As stated previously, more than 40% of the compounds in clinical trial fail due to poor (bio)pharmaceutical properties (solubility, log P, log D, chemical stability, permeability, metabolism, protein binding, plasma stability, etc.). A lot of efforts are now made to calculate or predict these properties in an early stage of preclinical research to prevent disappointment and the loss of a lot of money farther downstream in the drug discovery process. 

Pharmacodynamics metabolism, protein binding, loading values... 

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... 

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Thornton-Manning, J. Appleton, M. L. Gonzalez, F. J. Yost, G. S. Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes correlation of 3-methyleneindolenine formation and protein binding. J. Pharmacol. Exp. Ther. 1996, 276, 21-29. 

Witschi and colleagues19 identified the requirement for metabolic activation of BHT in determining that radioactivity from 14C-labeled BHT became covalently bound to proteins in mouse lung. Both toxicity and protein binding were prevented when mice were treated with cytochrome P450 inhibitors, thereby indicating the... 

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

Some AEDs, especially phenytoin and valproate, are highly bound to plasma proteins. When interpreting a reported concentration for these drugs, it is important to remember that the value represents the total (i.e., bound and unbound) concentration in the blood. Because of differences in the metabolism of these drugs, the clinical effects of altered protein binding are different for different drugs. 

Normally, 88% to 92% of phenytoin is bound to plasma protein, leaving 8% to 12% unbound. The unbound component is able to leave the blood to produce the clinical effect in the CNS, produce dose-related side effects in the CNS and at other sites, distribute to other peripheral sites, and be metabolized. Certain patient groups are known to have decreased protein binding, resulting in an increased percentage of drug that is unbound. These patient groups include ... 

Due to the Michaelis-Menten metabolism of phenytoin, alterations in its protein binding will result in increased severity of dose-related adverse effects. In patients with suspected changes in protein binding, it is useful to measure unbound phenytoin concentrations. 

When valproate protein binding is altered, the risk for severe dose-related adverse effects is much less compared to phenytoin. Michaelis-Menten metabolism is not a factor with valproate, so hepatic enzymes are able to efficiently metabolize the additional unbound portion. 

Zonisamide Modulate sodium and calcium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 00-600 mg/day start at 100 mg/day and titrate upward as indicated by response Half-life 63 hours Apparent volume of distribution 1.45 L/kg Protein binding 40% Primary elimination route Hepatic Not established Dizziness, somnolence Metabolic acidosis, oligohidrosis, paresthesias, renal calculi... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Drugs can affect thyroid function in a number of ways.41 Effects of drugs on thyroid hormone protein binding, LT4 absorption, and metabolism have been discussed previously. Several commonly used medications can alter thyroid hormone secretion. 

Pharmacodynamics Duration 1-4 weeks Absorption IM slow Time to peak serum levels 12-24 hours Duration 15-24 hours Absorption IM slow Distribution Poor blood-brain barrier penetration, enters breast milk Metabolism =30% hepatic inactivation Protein binding 65% Time to peak serum levels 1-4 hours Excretion Urine (60-90% as unchanged drug) Clearance Renal... 

As amisulpride has no hepatic metabolism, low protein binding, and is directly excreted in urine, there is little reason to suspect pharmacokinetic ethnic differences. Of course body mass and pharmacodynamic differences might occur, but to date have received little investigative attention. 

Biological factors that may influence pharmacological response and side effects include pharmacokinetics such as protein binding, distribution, metabolism, or... 

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