General pharmacology of cyclophosphamide


Cyclophosphamide is a synthetic anticancer drug. Its chemical name is 2-[Bis (2-chloroethyl) amino] tetrahydro-2H-1, 3, 2-oxazaphosphorine 2-oxide monohydrate.


Its molecular formula is  C7H15Cl2N2O2P and molecular weight is 261.1


The structural formula of cyclophosphamide is:

Structural formula of cyclophosphamide


After oral administration, it is rapidly absorbed by the gastrointestinal tract with a bioavailability of nearly 90% that means nearly 90% of cyclophosphamide reach in the systemic circulation. Peak concentrations of cyclophosphamide in blood occurred at 1 hour and peak concentrations of its metabolites occurred at 2-3 hours. Onset of action is 2-3 hours.


Cyclophosphamide is distributed throughout the body including brain, cerebrospinal fluid (CSF), breast milk and saliva. Approximately 20% of cyclophosphamide is bound to plasma proteins; however, about 60% of its metabolites are bound to plasma proteins. Volume of distribution is approximately 0.5-0.7 Liter/kg.


Cyclophosphamide requires metabolic activation before it can act as an anticancer agent.  Liver is the major site for metabolic activation of this drug, although activation may occur in other tissues. In the liver, it is metabolized by the cytochrome P450 system into phosphoramide mustard, and acrolein. These metabolites mainly phosphoramide mustard interfere with the growth of susceptible rapidly proliferating cancer cells.


Cyclophosphamide is excreted exclusively in urine primarily in the form of metabolites, but from 10 to 20% of drug is excreted in urine as unchanged form. The excretion half-life ranges from 4-6 hours.