Protein bound drugs

Those taking multiple highly protein-bound drugs... 

J. Serum albumin concentration T Vd protein-bounde drugs... 

Lipophilic drugs (e.g., opiates and antibiotics) cross more easily than do water-soluble drugs. Certain protein-bound drugs may achieve higher plasma concentrations in the fetus than in the mother. 

T or si Free fraction of highly plasma protein-bound drugs si Clearance and T t1/2 for some oxidatively metabolized drugs si Clearance and T t1/2 for drugs with high hepatic extraction ratios si Clearance and T t 2 for renally eliminated drugs and active metabolites... 

Plasma protein-bound drugs that are substrates for transport carriers can be cleared from blood at great velocity, e.g., p-aminohippurate by the renal tubule and sulfobromophthalein by the liver. Clearance rates of these substances can be used to determine renal or hepatic blood flow. 

Highly protein-bound drugs In vivo, raloxifene did not affect the binding of warfarin, phenytoin, or tamoxifen. However, use caution when raloxifene is coadministered with other highly protein-bound drugs, such as diazepam, diazoxide, and lidocaine. 

Distribution - Valproic acid is rapidly distributed. Volume of distribution of total or free valproic acid is 11 or 92 L/1.73 m, respectively. Valproic acid has been detected in CSF (approximately 10% of total concentrations) and milk (about 1% to 10% of serum concentrations). Therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. The plasma protein binding of valproate is concentration-dependent. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (eg, aspirin). Conversely, valproate may displace certain protein-bound drugs (eg, phenytoin, carbamazepine, warfarin, tolbutamide). 

Use caution when administering atovaquone concurrently with other highly plasma protein bound drugs with narrow therapeutic indices as competition for binding sites may occur. 

These active secretory systems are important in drug excretion because charged anions and cations are often strongly bound to plasma proteins and therefore are not readily available for excretion by filtration. However, since the protein binding is usually reversible, the active secretory systems can rapidly and efficiently remove many protein-bound drugs from the blood and transport them into tubular fluid. 

The acidic NSAIDs include the salicylates and an increasing number of other compounds. The latter agents, as a group, share many common properties they may have toxicities, are highly protein bound and have the potential for interacting with other protein-bound drugs. The choice of a particular agent often depends on the reaction of the patient. Table 36.3 illustrates pharmacokinetic properties of selected NSAIDs. 

The SSRIs bind tightly to plasma proteins and may interfere with other protein-bound drugs (e.g., warfarin, digitoxin), causing a shift in plasma concentrations that can potentially result in adverse effects (Schrefer, 2001). As mentioned above, the SSRI medications can... 

In contrast to other protein-bound drugs for which a loading dose is given to achieve rapid steady-state... 

For sample preparation, the I.S. (d7-TACA) was spiked into each 1 mL portion of porcine plasma sample to a concentration of 100 pg/mL then mixed 1 1 (v v) with 4 % phosphoric acid to release protein-bound drugs. SPE cartridges were preconditioned as described above, after sample loading, optimized SPE wash and elution methods were applied for sample extraction. 

The ultracentrifugation (UC) method achieves separation of free and protein bound drugs by centrifugation of the sample in a tube without a membrane. It makes use of the fact that sedimentation of solutes depends upon their molecular weight. The first time Steinberg and Schachmann (1966) demonstrated theoretically and practically the potential of the method. 

It is evident that displacement of even small amounts of extensively protein-bound drugs can result in a relatively large increase in the active fraction. This commensurate rise in the therapeutic effect often leads to an undesirable... 

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