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CH2-1-pyrrolidinyl

'Bisphosphonates approved for use in nonmalignant conditions. Bisphosphonates approved for use in malignancy for one or more indications. Other agents are only available for experimental purposes.

'Bisphosphonates approved for use in nonmalignant conditions. Bisphosphonates approved for use in malignancy for one or more indications. Other agents are only available for experimental purposes.

(Table 1). The biological activity is dependent on the R2 side chain. The various structures in this class are given in Table 1. Being very hydrophilic they have poor and variable bioavailability, hence binding to food components is important clinically.

With penicillamine whose structure is shown in the following figure, there should be no surprise at chelation with components in food, as its primary mode of action is through chelation of copper in Wilson's disease. Iron is among the metals thus affected. When iron and penicillamine are taken together, chelation of penicillamine by iron in the gut reduces its absorption and activity.

(CH3)sC—CHCOOH Penicillamine

Orally administered iron has been shown to reduce the effects of penicillamine. A period of at least two hours, or preferably eight hours, should elapse between administration of penicillamine and iron supplements or other iron-containing products. Penicillamine can also bind zinc, and this interferes with the absorption of both the drug and the metal.

Normal dietary intake can significantly interfere with penicillamine absorption. In one study penicillamine levels were reduced to 52% of those from the fasting dose after food (12,13).

Chelation with Dairy Products

The quinolones have the requisite binding structures as can be seen in the following diagrams of ciprofloxacin and norfloxacin, namely the adjacent C=O and -OH groups.

Norfloxacin Quinolone dimer-metal ion chelate

The presumed structure of a dimer-metal ion chelate is shown above (14). This effective size increase through the linking of two quinolones molecules is one reason for reduced absorption.

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