Zidovudine and stavudine are nucleoside reverse transcriptase inhibitors (NRTIs) that combat HIV by interfering with viral replication. Specifically, they act as nucleotide analogs. Zidovudine (AZT) is phosphorylated intracellularly to its active triphosphate form, AZTTP. This then competes with deoxynucleotide triphosphates (dNTPs) for incorporation into the growing viral DNA chain by reverse transcriptase. The incorporation of AZTTP terminates DNA chain elongation, preventing further viral replication.
Zidovudine Pharmacokinetics
Zidovudine is absorbed orally with bioavailability around 60-70%. Peak plasma concentrations are achieved within 1-2 hours. It’s extensively metabolized in the liver, primarily by glucuronidation. Elimination occurs primarily through renal excretion. The half-life is approximately 1 hour. Dosage adjustments are needed for renal impairment.
Stavudine Pharmacokinetics
Stavudine (d4T) follows a similar mechanism of action as zidovudine, also requiring intracellular phosphorylation to its active triphosphate form for incorporation into viral DNA. However, stavudine’s oral bioavailability is higher, around 86%. Peak plasma concentrations are reached within 1-2 hours. Its metabolism involves primarily glucuronidation and hepatic oxidation. Renal excretion is the major route of elimination. The half-life of stavudine is around 1.5 hours.
Differences in pharmacokinetic profiles, such as bioavailability and half-life, influence dosing regimens and potential drug interactions. Careful monitoring is crucial for optimal therapeutic efficacy and minimization of adverse events. Consult appropriate guidelines and resources for specific dosage recommendations and adjustments.
