Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir.

摘要: Cidofovir and adefovir are members of a new class antiviral compounds. They acyclic phosphonate analogues deoxynucleoside monophosphates. Both compounds undergo intracellular activation to form diphosphates that potent inhibitors viral DNA polymerases. has broad spectrum activity against herpesviruses, papillomaviruses poxviruses, whereas retroviruses certain viruses, including herpesviruses hepadnaviruses. Intravenous cidofovir is approved for treatment cytomegalovirus retinitis in patients with AIDS. dianionic at physiological pH have low oral bioavailability animals humans. After intravenous administration HIV-infected patients, the pharmacokinetics both drugs independent dose consistent preclinical data. Systemic exposure proportional cleared by kidney excreted extensively as unchanged drug urine. Intracellular small fraction ( 90% an recovered urine over 24 hours. Metabolism does not contribute significantly total clearance either drug. Concomitant probenecid decreases renal incidence nephrotoxicity, presumably blocking its active tubular secretion. This basis clinical use concomitant nephroprotectant during therapy. Subcutaneous produces equivalent following administration. Drug interaction studies ongoing, but there no evidence between zidovudine or adefovir. Clearance impairment showed linear relationship creatinine clearance. The led development prodrug, dipivoxil, currently HIV hepatitis B infections.