Pharmacokinetics protein binding

Solution equilibria for gadolinium imaging agents have been studied with consideration for pharmacokinetic, protein binding, elimination, and safety aspects of the dmgs. The thermodynamic stability constant, Kq defined by equation 7.4 must be large for clinically viable agents. Some Kq l data are listed in Table 7.3. 

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

Pharmacokinetics Protein binding 90%. Widely distributed. Metabolic fate unknown. Cleared bynonrenal pathways. Minimal removal by hemodialysis. Amphotec and Abelcet are not dialyzable. Amphotec Half-life 26-28 hr. Abelcet Half-life 7.2 days. AmBisome Half-life 100-153 hr. 

Pharmacokinetics Protein binding 28%-38%. Widely distributed. Partially metabolized in the liver. Primarily excreted in urine. Removed by hemodialysis. Half-life 1 hr (increased in impaired renal function). 

Mecfianism of Action A methylxanthine and competitive inhibitor of phosphodiesterase that blocks antagonism of adenosine receptors. Therapeutic Effect Stimulates respiratory center, increases minute ventilation, decreases threshold of or increases response to hypercapnia, increases skeletal muscle tone, decreases diaphragmatic fatigue, increases metabolic rate, and increases oxygen consumption. Pharmacokinetics Protein binding 36%. Widely distributed through the tissues and CSF. Metabolized in liver. Excreted in urine. Half-life 3-7 hr. 

Pharmacokinetics Protein binding less than 6%. Excreted primarily unchanged in urine. Effect of hemodialysis unknown. Elimination half-life 1.4-3.8 hr. 

Pharmacokinetics Protein binding 25%. Excreted in urine. Half-life 2.5 hr. Available Forms ... 

Pharmacokinetics Protein binding low. Rapidly distributes to total body water after IV infusion. Extensively metabolized by the liver. Minimal excretion in the urine. Removed by hemodialysis. Half-life 5 hr. 

Mecfianism of Action A prostaglandin that dilates systemic and pulmonary arterial vascular beds, alters pulmonary vascular resistance, and suppresses vascular smooth muscle proliferation. Therapeutic Effect Improves symptoms and exercise tolerance in patients with pulmonary hypertension delays deterioration of condition. Pharmacokinetics Protein binding 60%. Metabolized in liver. Primarily excreted in urine minimal elimination in feces. Half-life 20-30 min. 

Pharmacokinetics Protein binding 76%. Partial elimination in feces minimal excretion in urine. Not removed by hemodialysis. Half-life 11-12 hr (oral capsule). 

Pharmacokinetics Protein binding-. 52%. Metabolized in liver. Eliminated in urine. Half-life 40 hr. 

Mechanism of Action An antihyperlipidemicthat interferes with cholesterol biosynthesis by inhibiting the conversion of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate, a precursor to cholesterol. Therapeutic Effect Decreases LDL cholesterol, VLDL, and plasma triglyceride levels, increases HDL concentration. Pharmacokinetics Protein binding 88%. Minimal hepatic metabolism. Primarily eliminated in the feces. Half-life 19 hr (increased in patients with severe renal dysfunction). 

Mechanism of Action Aketolide that blocks protein synthesis by binding to ribosomal receptor sites on the bacterial cell wall. Therapeutic Effect Bactericidal. Pharmacokinetics Protein binding 60%-70%. More of drug is concentrated in WBCs than in plasma, and drug is eliminated more slowly fromWBCs than from plasma. Partially metabolized by the liver. Minimally excreted in feces and urine. Half-life 10 hr. 

Pharmacokinetics Protein binding 55%. Metabolism and elimination are not known. Half-life 5-7 hr. 

Pharmacokinetics Protein binding 22%. Not metabolized. More than 95% excreted in urine. Half-life 167 hr. 

Urographic contrast agents are contrast agents which possess the characteristics of very little enteral absotp-tion, almost no protein binding or uptake into cells, an extracellular (interstitial) distribution and glomerular filtration. These pharmacokinetics are due to very little interaction with the organism, resulting in very low toxicity, preferably nonionic (neutral) molecules. 

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. 

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... 

T. F. Blaschke, Protein binding and kinetics of drugs in liver disease, Clin. Pharmacokinet, 2, 32-44 (1977). 

L. Notarianni, Plasma protein binding of drugs in pregnancy and in neonates, Clin. Pharmacokinet, 18, 20 (1990). 

Figure 3.1 shows the appearance of dihydromethysticin in the acceptor well as a function of time [15], The solid curve is a least-squares fit of the data points to Eq. (1), with the parameters Pe = 32 x 10-6 cm s 1, R = 0.42, and t s = 35 min. The membrane retention, R, is often stated as a mole percentage (%R) of the sample (rather than a fraction). Its value can at times be very high - up to 90% for chlor-promazine and 70% for phenazopyridine, when 2% wt/vol DOPC in dodecane is used. Figure 3.2 shows a plot of log %R versus log Ka(7.4), the octanol/water apparent partition coefficient. It appears that retention is due to the lipophilicity of molecules this may be a good predictor of the pharmacokinetic volume of distribution or of 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. 

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