DDI
DDI
also known as didanosine is a purine nucleoside that is the structural analogue
to deoxyadenosine. However, DDI differes from deoxyadenosine in DNA by one
single 3’-hydroxyl group the DDI group contains a hydrogen substituent [2].
DDI was approved for use by the FDA in 1991 and has been used as an
antiretroviral agent ever since. Didanosine differs from AZT in its use since it
is used in combination with other antiretroviral drugs instead of for
mono-therapeutic uses. Like AZT, DDI can be used in both adults and children.
DDI
is usually taken by mouth and absorbed rapidly in the small intestine. The peak
plasma concentrations are ranged between 15 minutess to approximately 2 hours.
However the amount of DDI absorbed depends on various factors, from the amount
of food in a patient’s stomach to the pH of the patient’s gastric juice. However, due to the fact a patients gastric secretions may
cause DDI to be inactivated, it must either be taken as an acid buffer coated
tablet or along with an antacid. Upon entering the stomach, a time release
effect occurs as the coated capsule release pellets of DDI that do not get
digested and enter the small intestine where absorption occurs.
DDI works by being converted by cellular enzymes into didieoxyadenosine 5’-triphosphateor ddA- TP. This metabolite of DDI works by inhibiting the HIV substrate deoxyadenosine 5’-triphosphate that HIV uses to make copies. Once ddA-TP enters the host’s cellular DNA, viral DNA synthesis is immediately halted. DDI is secreted into the CSF, cerebrospinal fluid, through the blood brain barrier with and typical can at times average up to 50% of all concentrations in the CSF up to an hour after an oral dose. The drugs metabolites are distributed through out the bloodstream until elimination by the kidneys and liver. The drug is eliminated through filtration by the glomerulus and exits through the patient’s urine. However, it is still uncertain if DDI and its metabolites are truly eliminated in a safe manner or if they are distributed into human milk. DDI’s half life is inversely proportional to the amount of creatinine that clears the body at the site of elimination. The greater the amount of creatinine clearance results in a smaller half-life quantity for didanosine, as result patients with advanced to moderate renal failure have a greater chance of missing out on the antiviral benefits of DDI.
Side Effects of DDI: