Chemo Secrets From a Breast Cancer Survivor

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To be clinically useful, a chemotherapeutic drug must have both selective toxicity against pathogens and fa vorable pharmacokinetics. The processes of absorption, distribution, metabolism, and elimination compose a drug's pharmacokinetics. The concentration of the drug in a patient's body as a function of time is determined by the dose administered and the drug's pharmacoki-netics in that patient.

Absorption from the gastrointestinal tract can be affected by other drugs and by food. Aluminum, calcium, and magnesium ions in antacids or dairy products form insoluble chelates with all tetracyclines and inhibit their absorption. Food inhibits tetracycline absorption but enhances doxycycline absorption; food delays but does not diminish metronidazole absorption; fatty food enhances griseofulvin absorption.

The chemical structure of a drug determines which enzymes metabolize it; a drug that fails to cross the cell membrane because of its polarity or size will be unme-tabolized even if biochemically active degradative enzymes are present in the cytosol. Systemic use of drugs that are poorly absorbed or are destroyed by the gastrointestinal environment requires parenteral administration. Of course, if the goal is to attack pathogens in the gastrointestinal tract, then poor gastrointestinal absorption may be an advantage.

An antibiotic drug that is itself nontoxic may have metabolites that are toxic, diminishing its usefulness. For example, imipenem is hydrolyzed by renal dipeptidase to a metabolite that is inactive against bacteria but is toxic to humans. Coadministration of cilastatin inhibits the renal dipeptidase, which both prevents the formation of the toxic metabolite and decreases imipenem clearance, prolonging the half-life of the drug.

Partitioning of some drugs into cells occurs. Red blood cells parasitized by malaria selectively take up chloroquine, which accounts in part for the efficacy of this antimalarial against intracellular malarial forms. The intrahepatocellular concentration of chloroquine is 500 times that of the blood plasma concentration. Macrolides and fluoroquinolones are also selectively partitioned into cells, which accounts in part for their efficacy against mycoplasma and chlamydia, both intra-cellular pathogens.

Extensive protein binding of a drug decreases its free level and decreases the compound's glomerular filtration. Because protein binding is reversible, bound drug and free drug are in dynamic equilibrium; thus protein binding determines the optimal dose and dosing interval of the drug. A drug's pharmacokinetic properties are an important source of variation in the clinical response of patients to chemotherapy.

As mentioned earlier, pharmacokinetics is not solely the property of a drug but instead is the consequence of interactions between the drug and the physiology of the patient. Thus, statements like "the half-life of gentam-icin is 2 hours" are not very useful, as the half-life is likely be longer or shorter in a given individual patient.

Individualization of dosing of chemotherapeutic drugs with a low therapeutic index is essential to effective, safe chemotherapy.

The concentrations of chemotherapeutic drugs in blood plasma, cerebrospinal fluid, urine, or ascites fluid can be measured to determine whether sufficient drug is present to inhibit or kill a given pathogen and to ensure that the concentration is not so high as to be toxic to the patient.

In severe bacterial infections that are difficult to eradicate, such as endocarditis or osteomyelitis, it may be important to ensure that the patient's serum remains bactericidal at the lowest, or trough, concentration in the dosing interval. Dilutions of patient's serum can be incubated with the organism isolated from the patient and the minimum bactericidal concentration determined through serial dilutions. Treatment is considered adequate if the serum remains bactericidal at a dilution of 1:8.

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