Human Plasma Proteins

Plasma protein fractions include human plasma protein fraction 5% and normal serum albumin 5% (Albuminar-5, Buminate 5%) and 25% (Albuminar-25, Buminate 25%). Plasma protein fraction 5% is an IV solution containing 5% human plasma proteins. Serum albumin is obtained from donated whole blood and is a protein found in plasma The albumin fraction of human blood acts to maintain plasma colloid osmotic pressure and as a carrier of intermediate metabolites in the transport and exchange of tissue products. It is critical in regulating the volume of circulating blood. When blood is lost from shock, such as in hemorrhage, there is a reduced plasma volume. When blood volume is reduced, albumin quickly restores the volume in most situations. 

Lobell M and Sivarajah V. In silico prediction of aqueous solubility, human plasma protein binding and volume of distribution of compounds from calculated pKa and AlogP98 values. Mol Divers 2003 7 69-87. 

Parent drug is bound to bovine and human plasma proteins to an extent of 89 - 96 % (in vitro concentration range 0.2 -80 pg/ml) and exerts a pronounced affinity to various tissues. 

L17. Lukas, D. S., and De Martino, A. G., Binding of digitoxin and some related cardenolides to human plasma proteins. J. Clin. Invest. 48, 1041-1053 (1969). 

Distribution - The volume of distribution of the drug in the central compartment is approximately 14 L per 70 kg ideal body weight. Treprostinil was 91% bound to human plasma protein. 

Distribution - Ezetimibe and ezetimibe-glucuronide are highly bound (greater than 90%) to human plasma proteins. 

Absorption - After oral administration, peak plasma levels are reached within 3 to 8 hours. The absolute bioavailability of solifenacin is approximately 90%, and plasma concentrations are proportional to the dose administered. Distribution - Solifenacin is approximately 98% bound to human plasma proteins, principally to i-acid glycoprotein. 

Metaboiism/Excretion- Nefazodone is extensively metabolized after oral administration by less than 1% is excreted unchanged in urine. The mean half-life ranged between 11 and 24 hours. Nefazodone is extensively (more than 99%) bound to human plasma proteins in vitro. 

Distribution - Following multiple dose administration, steady state is reached within 15 days. Donepezil is approximately 96% bound to human plasma proteins. 

Metabolism/Excretion - Lamotrigine is approximately 55% bound to human plasma proteins. Following multiple administrations to healthy volunteers taking no other medications, lamotrigine induced its own metabolism resulting in a 25% decrease in half-life and a 37% increase in plasma clearance. 

Steady state is reached in approximately 4 days in patients with normal renal function. Topiramate is 15% to 41% bound to human plasma proteins over the concentration range of 0.5 to 250 mcg/mL. 

Pharmacokinetics Following oral administration to healthy volunteers, mean peak plasma concentrations were achieved within 3 hours. Bupropion is 84% bound to human plasma proteins in vitro. Bupropion is extensively metabolized with a mean... 

Distribution - The binding of balsalazide to human plasma proteins was at least 99%. 

Distribution - Daptomycin is reversibly bound to human plasma proteins, primarily to serum albumin, in a concentration-independent manner. The mean serum protein binding of daptomycin was approximately 92% in healthy adults. 

Distribution - The binding of oseltamivir carboxylate to human plasma protein is low (3%). The binding of oseltamivir to human plasma protein is 42%, which is insufficient to cause significant displacement-based drug interactions. /Wefabo//sm- Oseltamivir is extensively converted to oseltamivir carboxylate by... 

Distribution - Indinavir was approximately 60% bound to human plasma proteins over a concentration range of 81 to 16,300 nM. 

Distribution - The apparent volume of distribution after IV administration of abacavir was approximately 0.86 L/kg. Binding to human plasma proteins is approximately 50%. 

Pharmacokinetics Following oral administration, abacavir, lamivudine, and zidovudine are rapidly absorbed and extensively distributed. Binding of abacavir to human plasma proteins is about 50% binding of lamivudine and zidovudine to plasma proteins is low. 

Distribution - Binding of emtricitabine to human plasma proteins was less than 4%. 

Distribution - The mean volume of distribution is 12 L/kg. Sirolimus is extensively bound (approximately 92%) to human plasma proteins. The binding of sirolimus was shown mainly to be associated with serum albumin (97%), - -acid glycoprotein, and lipoproteins. The majority of sirolimus is... 

Moda, T.L., Montanari, C.A., Andricopulo, A.D. In silico prediction of human plasma protein binding using hologram QSAR. Lett. Drug Des. Discov. 2007, 4, 502-9. 

Sazuka, M., Itoi, T., Suzuki, Y., Odani, S., Koide, T., and Isemura, M., Evidence for the interaction between (—)-epigallocatechin gallate and human plasma proteins fibronectin, fibrinogen, and histidine-rich glycoprotein, Biosci. Biotechnol. Biochem., 60, 1317, 1996. 

Boulton, D.W., Walle, U.K., and Walle, T., Extensive binding of the bioflavonoid quercetin to human plasma proteins, J. Pharm. Pharmacol., 50, 243, 1998. 

Pharmacokinetics According to the product label, the pharmacokinetics of eptihbatide are linear and dose proportional. Plasma elimination half-life is approximately 2.5 hours. The extent of eptihbatide binding to human plasma protein is about 25% its mean volume of distribution is 185mPkg. Clearance in patients with coronary artery disease is 55-58 ml/kg per hour. Clinical studies have included 2418 patients with serum creatinine between 1.0 and 2.0mg/dl without dose adjustment. No data are available in patients with more severe degrees of renal impairment, but plasma eptihbatide levels are expected to be higher in such patients. Patients in clinical studies were older than the subjects in clinical pharmacology studies, and they had lower total body eptihbatide clearance and higher eptihbatide plasma levels. Men and women showed no important differences in the pharmacokinetics of eptihbatide. 

The packing material first described for direct injection of biological samples was prepared by simply saturating the accessible adsorption sites of a Cis reversed-phase silica with human plasma proteins (105). After saturation, the human plasma proteins were denatured at the external surface, and their native conformation was destroyed. With this treatment, the proteins formed a hydrophilic layer with weak ion-exchange properties, which provided protection from contact with the sample proteins, whereas the alkyl ligands inside the pores remained unchanged and thus served for analyte retention. The retention behavior of the saturated phase did not alter with this treatment, but the efficiency was reduced dramatically. Such protein-coated columns have shown a lifetime of several months (106). 

Laycock, C. A, Phelan M. J. I Bucknall, R. C., and Coleman J W. (1994) A western blot approach to detection of human plasma protein conjugates derived from D-penicillamine. Ann Rheum Dis 53, 256-260... 

Zj -Acid glycoprotein or orosomucoid is a human plasma protein and present in 55-140 mg/mL of human plasma. It is a glycoprotein with 181 amino acids and has a molecular mass of 41,000. It is acidic in nature, with an isoelectric point of 2.7. It is a stable protein with two disulfide bridges. It also contains 40 sialic acid residues. The sialic acid residues bind with ammonium-type compounds at neutral pH and are essential for the enantioselective process. 

The steady-state volume of distribution is 12 1/kg. Donepezil hydrochloride is approximately 96% bound to human plasma proteins. The distribution of donepezil hydrochloride in various body tissues has not been definitively studied. However, in a mass balance study conducted in healthy male volunteers, 240 h after the administration of a single 5 mg dose of 14C-labeled donepezil hydrochloride, approximately 28% of the label remained unrecovered. This suggests that donepezil and/or its metabolites may persist in the body for more than 10 days. 

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