Drug Breakdown: AZT / Abacavir

Day 1: Seven days of nucleoside reverse transcriptase inhibitors (NRTIs), inspired by #ItsASin. The first HIV/AIDs drug #AZT (zidovudine) was discovered from unusual RNA/DNA elements found in marine sponges in the 1950s. Such analogues drew attention as anticancer drugs, because of the ability to disrupt cell function.

(cont) Abandoned as ineffective for cancer, #AZT was rediscovered during the frantic search for an HIV/AIDs treatment and was licensed by the FDA in 1987. #AZT was given in high doses, causing some toxicity. Resistance also became problematic. However, it did prolong life.

Day 2: It took a further decade to develop the combination drugs now standard therapy, as effective suppressors of HIV replication and also contain drug resistance. Newer versions of NRTIs eg #abacavir are the focus of this series.

Day 3: #abacavir kinetics: good oral bioavailability and tissue penetration eg into the CNS. Hepatic metabolism by alcohol dehydrogenase and glucuronidation, but no significant CYP450 activity. Avoid in moderate-severe liver impairment. Mostly renal excretion of metabolites, dosage reduction end stage renal failure. t½ ~ 1.5 hours.