Absorption plasma protein binding

Pharmacokinetics (including metabolism, as appropriate, and absorption, plasma protein binding, distribution, and elimination)... 

Penicillin Source Acid Resistance Oral Absorption (%) Plasma Protein Binding (%) p-Lactamase Resistance (S. aureus) Spectrum of Activity ainical Use... 

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]. 

Above 5 Low solubility and poor oral bioavailability. Erratic absorption. High metabolic liability, although potency may still be high. Basic amines tend to show high to very high Vd (Volume of distribution = ratio of overall tissue binding to plasma protein binding)... 

The original proposal of the approach, supported by a Monte Carlo simulation study [36], has been further validated with both pre-clinical [38, 39] and clinical studies [40]. It has been shown to be robust and accurate, and is not highly dependent on the models used to fit the data. The method can give poor estimates of absorption or bioavailability in two sets of circumstances (i) when the compound shows nonlinear pharmacokinetics, which may happen when the plasma protein binding is nonlinear, or when the compound has cardiovascular activity that changes blood flow in a concentration-dependent manner or (ii) when the rate of absorption is slow, and hence flip-flop kinetics are observed, i.e., when the apparent terminal half-life is governed by the rate of drug input. 

As described above, it will be normal to assume that the dose interval is 24 hours, i.e., once-a-day dosing. Absorption can be estimated with good confidence from absorption in the rat (see Section 6.1). Clearance is the sum of the predicted hepatic, renal, biliary and extrahepatic clearance. Hepatic clearance can be derived from in vitro studies with the appropriate human system, using either microsomes or hepatocytes. We prefer to use an approach based on that described by Houston and Carlile [83], Renal clearance can be predicted allometrically (see section 6.8.1). The other two potential methods of clearance are difficult to predict. To minimize the risks, animal studies can be used to select compounds that show little or no potential for clearance by these routes. As volume can be predicted from that measured in the dog, after correction for human and dog plasma protein binding (see Section 6.2), it is possible to make predictions for all of the important parameters necessary. 

Absorption/Distribution - Oral absorption is nearly complete. Peak plasma levels are attained at approximately 3 hours. The plasma half-life ranges from 12 to 27 hours after multiple oral doses. Steady-state levels are approached in 3 to 5 days once at steady-state, no accumulation occurs during chronic therapy. Plasma levels are approximately proportional to dose. In patients with congestive heart failure (CHF NYHA class III), the rate of flecainide elimination from plasma is moderately slower than for healthy subjects. Plasma protein binding is about 40% and is independent of plasma drug level over the range of 0.015 to about 3.4 mcg/mL. 

Absorption/Distribution - Memantine is highly absorbed with peak concentrations reached in approximately 3 to 7 hours. The mean volume of distribution is 9 to 11 L/kg and the plasma protein binding is low (45%). 

Absorption/Distributton - Galantamine is rapidly and completely absorbed with time-to-peak concentration in about 1 hour. Galantamine has an absolute oral bioavailability of about 90%. The plasma protein binding of galantamine is 18%. 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Absorption/Distribution - Bioavailability depends on an acidic pH for dissolution and absorption. In vitro, plasma protein binding is approximately 95% to 99%, mainly to albumin. 

Absorption/Distribution - When acyclovir was administered to adults at 5 mg/kg by 1 hour infusions every 8 hours, mean steady-state peak and trough concentrations were 9.8 mcg/mL and 0.7 mcg/mL, respectively. When acyclovir was administered to adults at 10 mg/kg by 1 hour infusions every 8 hours, mean steady-state peak and trough concentrations were 22.9 mcg/mL and 1.9 mcg/mL, respectively. Absorption is unaffected by food. Bioavailability is between 10% and 20% and decreases with increasing doses. Concentrations achieved in CSF are approximately 50% of plasma values. Plasma protein binding is 9% to 33%. Acyclovir distributes widely in... 

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

Abbreviations Sol, aqueous solubility F, bioavailability PPB, plasma protein binding Met, metabolism Tox, toxicity PA, passive absorption AP, apparent permeability. 

Sodium valproate is converted to valproic acid in the intestine and the acid is absorbed. Absorption may be delayed by food or by enteric-coated tablets. Valproic acid has a low volume of distribution and high plasma protein binding. In the elderly there is a risk for increased free valproic acid concentrations requiring lower doses and plasma concentrations at the lower therapeutic range. However it should be realized that these plasma concentrations do not correlate very well with the therapeutic or toxic effects and careful observation for symptoms is mandatory. 

Absorption after oral administration is incomplete and variable. Its bioavailability ranges from 20% to 50%. Cyclosporine can also be given intravenously. Plasma protein binding is about 90% and cyclosporine also accumulates in red blood cells. It is extensively metabolized in the gastrointestinal mucosa and in the liver by the cytochrome P450-enzyme system. Its elimination half-life is about 19 hours in adults with a range of 10-27 hours and about 9 hours in children with a range of 3-19 hours. Over 30 different metabolites have been... 

Many drugs interact with folate to affect its absorption, antagonize its biochemical activity, or increase its loss from the body. These drugs include ethanol, phenytoin, and oral contraceptives. Salicylates can compete with foUc acid for plasma protein binding. Methotrexate, a cytotoxic agent, is a folate antagonist that inhibits the biosynthesis of this coenzyme. 

The pharmacokinetics of stimulants are characterized by rapid absorption, low plasma protein binding, and quick extracellular metabolism (Patrick et al., 1987). Although some investigators claim that the dose-response relationship is affected by the child s weight, others have shown that individual dose-response stimulant effects are independent of the child s weight (Rapport et al., 1989). 

It decreases digoxin renal excretion It decreases digoxin plasma protein binding It decreases digoxin intestinal absorption It decreases digoxin sensitivity at its site of action... 

Among the cardiac glycosides, digitoxin is absorbed rapidly and completely from the gastrointestinal tract with oral absorption of approximately 90 to 100 percent with plasma protein binding of approx. 95 percent with plasma half life of 5 to 7 days. It enters the liver cells where it is metabolised to epidigitoxigenin and is excreted in bile and urine. 

Alterations in plasma vitamin concentrations have been observed in oral contraceptive users, and attributed to reduced absorption and changes in plasma protein-binding capacity (177). 

Drugs may affect the absorption, distribution, metabolism, or excretion of other drugs. This includes those interactions in which the gastrointestinal absorption of a drug, plasma protein binding, drug metabolism, and urinary excretion are either enhanced or inhibited. 

---