Plasma proteins, partitioning

When 20 mg/kg of methimazole was administered i.p. or orally to rats, urinary methimazole glucuronides accounted for 36-48% of the dose in 24 hours. The only other urinary metabolite accounted for 10-20% and was not characterized. An additional 14-20% of methimazole was excreted unchanged in 24 hour urine. The bile contained methimazole glucuronide and two unidentified metabolites. One of which was the same as the unidentified urinary metabolites. Plasma proteins bound 5% of methimazole which had no affinity for any specific tissue. Methimazole had a much greater CHCI3/H2O partition coefficient and 1 0 solubility than did propylthiouracil. Between 77 and 95% of the methimazole was excreted in the urine and approximately 10% in the bile. Since fecal excretion was neglegible an enter-ohepatic circulation was present. The half life of urinary excretion was 5-7 hours regardless of the route of administration (15). 

A comprehensive piece of work on predicting VDSS from physiochemical data was reported by Poulin and Thiel for both rat and human [28]. The experimental input data required is the plasma protein binding, blood cell partitioning, octanokwater partition ratio, and olive oikwater partition ratio. The underlying relationship utilized was ... 

The specific mechanisms by which mirex and chlordecone are transferred from the gut, lungs, or skin to the blood are not known. However, mirex is a highly stable, lipophilic compound that is resistant to metabolism. It has a high lipid water partition coefficient, so it partitions readily into fat and demonstrates a very high potential for accumulation in tissues. The preferential distribution of chlordecone to the liver rather than to the fat tissue is due to its association with plasma proteins. 

Distribution - In vitro orlistat was greater than 99% bound to plasma proteins (lipoproteins and albumin were major binding proteins). Orlistat minimally partitioned into erythrocytes. 

The mean steady-state Vd following 12 mg IV is 700 L, suggesting saquinavir partitions into tissues. Saquinavir is approximately 98% bound to plasma proteins over a concentration range of 15 to 700 ng/mL. CSF levels are... 

S. Urien, E. Albengres, A. Comte, J. R. Kiechel, and J. P. Tillement, Plasma protein binding and erythrocyte partitioning of nicardipine in vitro. J. Cardiovasc. Pharmacol. 7 891-898 (1985). 

The major manufacturing process for plasma-derived products is the fractionation of human plasma, the liquid part of blood, to remove the minute amounts of plasma proteins present in each unit of plasma. To make the process commercially successful, very large quantities of plasma are mixed together and then fractionated. Dr. Elias Cohn developed the initial process in the early 1940s at Harvard University using differential cold alcohol precipitation. Essentially the same process (as modified by Oncley) is used today, with the addition of more rigorous viral inactivation techniques to increase safety. The conditions have been set to both efficiently fractionate the protein and to maximize viral partition, inactivation, or removal. Considering the... 

E. R. Garrett, K. Seyda, and P. Marroum, HPLC assays of the illicit design drug, Ecstasy, a modified amphetamine with applications to stability, partitioning and plasma protein binding, Acta Pharm. Nord., 3 9 (1991). 

V, steady-state volume of distribution referenced to the unbound drug in plasma. Kp, partition coefficient of drug between plasma protein and plasma water, r, ratio of the fractions of the drug non renally and renally eliminated. 

Novartis uses the In Silico Profiling web tool. Available properties include the octanol water partition coefficient log P, molar refractivity, flexibility index, hydrogen bonding characteristics and molecular polar surface area. Various drug properties, such as intestinal absorption, BBB permeability or Plasma Protein Binding (PPB) are calculated based on in-house models. 

Although diastereoisomers, both quinine and quinidine, have similar physical properties (Fig. 18). In clinical studies, the renal clearance of quinidine was fourfold greater than that of quinine (57). No stereoselective differences in plasma protein binding were observed. The renal filtration and passive reabsorption of these two diastereoisomers should be similar since the compounds have similar octanol-water partition coefficients and pKa values (57). Therefore, stereoselective active renal secretion may be the mechanism responsible for the observed differences in the renal clearances of quinine and quinidine. 

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