Drug-protein interactions, plasma

We hypothesize that a subtle drug protein interaction occurs when polar solvents are used to extract highly lipid soluble drugs from plasma. These solvents are capable of delipidizing lipoproteins. It is possible that, when delipidization occurs, the hydro-phobic region of that protein is exposed. The hydro-phobic region could then bind A9-THC and the binding... 

Drug Levels in Plasma. Drug levels may also be measured in a clinical trial. Such levels are usually part of a pharmacokinetic analysis but also provide important safety data. This information would be particularly relevant in cases of suspected or actual drug overdosage, drug interactions, to correlate medicine levels with toxic events, or in other situations. It must be clarified whether free levels of the drug and/or the protein bound will be measured by the laboratory. 

Drug-protein binding is the reversible interaction of drugs v/ith different proteins in plasma. Albumin is not the exclusive protein involved. Drugs bind to specific sites on the protein. 

The high affinity of many platinum compounds for sulfur and the availability of many sulfur-containing biomolecules have raised the question whether Pt-sulfur biomolecule interactions could serve as a drug reservoir for platination at DNA, necessary for the antitumor activity of cis-Pt. Two reaction paths are possible, i.e., spontaneous release of plantinum from the sulfur, or nucleophilic displacement of platinum from sulfur by guanine (N7), for example. At the moment, there is no real evidence for the existence of such reactivation mechanisms. In fact, it has been reported that Pt-protein interactions in the plasma (albumin) are not reversible under normal conditions (161, 165). Further, a mixture of cis-Pt-methionine products does not show antitumor properties (166), indicating no induced platination of DNA. More research is required to investigate the existence of a reactivation mechanism. However, it is predicted that if such a reactivation phenomenon is operational, the most likely candidate is the labile Pt-methionine bond, as has been shown by its rapid reaction with Naddtc, STS, and thiourea (vide supra) (131). 

Although there is no evidence that neuropsychiatric complications of macrolides develop more readily in uremic patients, several factors may predispose toward these adverse effects, such as reduced drug clearance, altered plasma protein binding, different penetration of drug across the blood-brain barrier, and an increased propensity for drug interactions. 

PENICILLINS ANTICANCER AND IMMUNOMODULATING DRUGS - METHOTREXATE t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Penicillins 1 renal elimination of methotrexate by renal tubular secretion, which is the main route of elimination of methotrexate. Penicillins compete with methotrexate for renal elimination. Displacement from protein-binding sites may occur and is only a minor contribution to the interaction Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasias, liver toxicity and pulmonary toxicity. Do FBCs and LFTs prior to concurrent treatment... 

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