Activity and protein binding

The conformational requirements for activity and protein binding were investigated with 2, 3 -dimethyl-3,5-diiodothyro-nine as the model for a distal conformer of T3 and 2,5f-dimethyl-3,5-diiodothyronine as the proximal model ( 1> 5 6). ... 

Witschi and colleagues19 identified the requirement for metabolic activation of BHT in determining that radioactivity from 14C-labeled BHT became covalently bound to proteins in mouse lung. Both toxicity and protein binding were prevented when mice were treated with cytochrome P450 inhibitors, thereby indicating the... 

These amino acid and protein binding results might account for the low toxic side effects of this class of anticancer agents (72). On the other hand, the relatively weak binding to amino acids and proteins could perhaps aid in transport and delivery of active species to cancer cells prior to binding to DNA or RNA (75). 

Animal experimental models of nickel-induced skin sensitivity are few and have been conducted only under very specialized conditions (USEPA 1986). Studies examining the mechanism of nickel contact sensitization and its extent in wildlife are needed (USPHS 1993). The importance of the surface properties and crystalline structure of nickel compounds in relation to their reactivity and protein-binding activities is well documented. It is therefore necessary to identify clearly the nickel compounds to which exposure occurs (Sunderman etal. 1984). Acute and chronic dermal and... 

Typically, in vitro tests are cell- or tissue-based experiments. The aim is to study the biochemical functions of the target as a result of binding to potential drug ligands. Parameters such as ionic concentrations, enzyme activities, and protein expression profiles are studied. 

Pharmacokinetics Rapidly hydrolyzed loan active metabolite. Protein binding 99%. Excreted in the urine, bile, and feces. Half-life 2-4 hr... 

Mectianism of Action An anticonvulsant that blocks sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repef if ive neuronal firing, and diminishing synapfic impulses. Therapeutic Effect Prevenfs seizures. Pharmacokinetics Complefely absorbed from GI tract and extensively metabolized in the liver to active metabolite. Protein binding 40%. Primarily excreted in urine. Half-life 2 hr metabolite, 6-10 hr. 

Circular dichroism Secondary structure of proteins, interaction between ligands and proteins, binding of metals at active sites in enzymes 1 )... 

Oral lacosamide is rapidly and completely absorbed in adults, with no food effect. Bioavailability is nearly 100%. The plasma concentrations are proportional up to 800 mg orally. Peak concentrations occur from 1 to 4 hours after oral dosing, with an elimination half-life of 13 hours. There are no active metabolites and protein binding is minimal. Lacosamide does not induce or inhibit cytochrome P450 isoenzymes, so drug interactions are negligible. 

The effects of DNA-binding transactivators on Pol II are mediated by coactivator protein complexes such as TFIID or mediator. The modular structures of the transactivators have distinct activation and DNA-binding domains. Other protein complexes, including histone acetyltransferases such as GCN5-ADA2-ADA3 and ATP-dependent complexes such as SWI/SNF and NURF, reversibly remodel chromatin structure. 

In patients with acute hepatitis and active hepatitis, protein binding of the glucocorticoids will be reduced and peak concentrations of administered glucocorticoids increased. Conversion of prednisone to prednisolone has been reported to be impaired in chronic active liver disease (409). However, although plasma prednisolone concentrations were more predictable after the administration of prednisolone than of prednisone to a group of healthy subjects (410), there was no difference in patients with chronic active hepatitis. There was also impaired elimination of prednisolone in these patients. In a review of the pharmacokinetics of prednisone and prednisolone it was concluded that fear of inadequate conversion of prednisone into prednisolone was not justified (411). Patients with hepatic disease suffer adrenal suppression more readily (111). 

Oral bioavailability exceeds 80% and is not food-dependent. Peak serum levels after standard doses are 1.5 0.5 g/mL, and protein binding is less than 36%. In children, the mean CSF plasma ratio of lamivudine was 0.2. Mean elimination half-life is 2.5 hours, while the intracellular half-life of the active 5 -triphosphate metabolite in HIV-1-infected cell lines is 10.5-15.5 hours. The majority of lamivudine is eliminated unchanged in the urine, and the dose should be reduced in patients with renal insufficiency or low body weight (Table 49-3). No supplemental doses are required after routine hemodialysis. 

---