User:Mpeng808/sandbox

Mechanism:

Lamivudine and zidovudine are both nucleoside reverse transcriptase inhibitors (NRTI). They are competitive inhibitors of reverse transcriptase to reduce the activity of reverse transcriptase (RT) causing HIV infected cells to decrease the number of viruses in the body. Lamivudine and zidovudine act as nucleoside analogs, which are substrates for the human enzyme, thymidine kinase (TK). The initial phosphorylation step is crucial for the drug’s activity by HIV enzymes, then phosphorylated by TK. Once converted into the active 5’-triphosphate form, the drug is then incorporated to the end of the growing chain of the viral DNA causing the chain to be terminated, where nucleotides can no longer be added to the growing viral DNA.

Lamividuine and zidovudine combination therapy is believed to work synergistically together to prevent mutations in the HIV virus, which can contribute to drug resistance.

Pharmacokinetics/pharmacodynamics

Lamivudine is well absorbed in the body and distributes widely into the extravascular space. Oral bioavailability is >80% and overall metabolism is insignificant where approximately 95% of the drug is found unchanged in the urine. The only known metabolite found in humans is trans-sulfoxide. The half-life of lamivudine is 10 to 15 hours and binds poorly to plasma proteins.

Zidovudine is well absorbed in the body and penetrates into the cerebrospinal fluid. Oral bioavailability is 75% and primarily metabolized by the liver by glucuronidation. The primary metabolite is GZDV, an inactive metabolite produced after first pass metabolism. The half-life of zidovudine is 0.5 to 3 hours and binds poorly to plasma proteins.

Lamivudine and zidovudine are not extensively metabolized by CYP450 liver enzymes.