Kinetics chemotherapeutic agents

Conra.d-Limpa.ch-KnorrSynthesis. When a P-keto ester is the carbonyl component of these pathways, two products are possible, and the regiochemistry can be optimized. Aniline reacts with ethyl acetoacetate below 100°C to form 3-anilinocrotonate (14), which is converted to 4-hydroxy-2-methylquinoline [607-67-0] by placing it in a preheated environment at 250°C. If the initial reaction takes place at 160°C, acetoacetanilide (15) forms and can be cyclized with concentrated sulfuric acid to 2-hydroxy-4-methylquinoline [607-66-9] (49). This example of kinetic vs thermodynamic control has been employed in the synthesis of many quinoline derivatives. They are useful as intermediates for the synthesis of chemotherapeutic agents (see Chemotherapeuticsanticancer). 

A third experiment examined 20% (w/w) BCNU loaded pCPP SA polymer release kinetics and biodistribution in a primate intracranial model. Tiunorcidal concentrations of BCNU spread up to 4 cm from the polymer implantation site 24 h post-operatively (86). Taken together, these animal studies established the drug delivery capabihties of pol3rmer technology, and confirmed the viabifity of local, sustained, and clinically significant in vivo delivery of chemotherapeutic agents within the CNS. 

The apparent volume of distribution (f ) (see Section 3.0), discloses whether the drug remains in one compartment (usually the blood stream) or is shared with a second compartment (usually the tissues). Chemotherapeutic agents work best if shared, because infection is commoner in the tissues than in blood. A two-compartment distribution can be confirmed by the biphasic character of the first-order plot of concentration against time. The symbol relates to any transfer from compartment i to compartment 2, whereas reverses the direction (examples of microscopic constants). Kinetics for two-compartment absorption were worked out by Loo and Riegelman (1968). The cardiac glycoside digoxin is typical of a two-compartment drug. With barbiturates, the second compartment is the tissue lipoid and not the tissue water. 

Most drugs produce a reversible pharmacological response. However, some antibiotics, irreversible enzyme inhibitors, and anticancer agents incorporate irreversibly or covalently into a cell s metabolic pathway. This results in an irreversible effect—cell death. Complex kinetic models are used to explain the relationship of dose-chemotherapeutic effects for some drugs, such as methotrexate, cyclophosphamide, and arabinosylcytosine.f ... 

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