TECHNOLOGY FOR IMPROVED ORAL DELIVERY OF ANTI-HIV DRUGS

THE LONG-TERM OBJECTIVE IS TO DEVELOP AN ORAL DRUG DELIVERY STRATEGY AND TECHNOLOGY BASE TO INCREASE THE EXTENT OF ABSORPTION AND DECREASE THE VARIABILITY OF THE ABSORPTION OF NUCLEOTIDE ANTIVIRAL DRUG ANALOGS IN HUMANS. 2', 3'-DIDEOXYINOSINE (VIDEX TM, DDI) IS A PURINE NUCLEOSIDEDRUG ANALOG THAT IS A POTENT AND SELECTIVE INHIBITOR OR HIV REVERSE TRANSCRIPTASE. DDI IS EXTREMELY UNSTABLE IN THE ACIDIC CONDITIONS OF THE STOMACH. HOWEVER, EVEN WHEN DDI IS GIVEN WITH ANTACIDS THE ABSORPTION IS HIGHLY VARIABLE IN HUMANS. DURING PHASE I, A DRUG DELIVERY STRATEGY WILL BE DEVELOPED BASED ON THE RESULTS OF INTESTINAL PERFUSION EXPERIMENTS IN RATS ANDON THE PHYSICO-CHEMICAL PROPERTIES OF DDI. BASED ON THOSE RESULTS A DOSAGE FORM FOR DDI WILL BE DEVELOPED AND TESTED IN DOGS. THE POTENTIAL BENEFITS OF IMPROVED DDI ORAL DELIVERY TO AIDS/ARC PATIENTS ARE A DECREASE IN SIDE EFFECTS AND AN IMPROVED AND CONSISTENT DELIVERY OF DDI LEADING TO REPRODUCIBLE PHARMACOKINETICS AND PHARMACODYNAMIC RESPONSE. THIS STRATEGY COULD REDUCE PATIENT TOXICITY, THUS IMPROVING AND PROLONGING ORAL THERAPY.