Absorption and elimination kinetics of zidovudine in the cerebrospinal fluid in HIV-1-infected patients.

Current knowledge of zidovudine (ZDV) levels in human cerebrospinal fluid (CSF) is limited to single sample determination and extrapolation to time after administration. Longitudinal studies have not been performed. Pharmacokinetic parameters of ZDV in CSF were determined in six HIV-1-infected patients. CSF samples were collected by an intraspinal catheter over a period of 6 hours after a single intravenous (IV) dose of ZDV (2.5 mg/kg). ZDV concentrations were measured by high-performance liquid chromatography (HPLC). ZDV was cleared rapidly from plasma, with a mean terminal elimination half-life (t 1/2) of 75.5 +/- 4.9 minutes. ZDV penetrated slowly into the CSF, reaching maximal concentration (Cmax) 2 hours after the start of the infusion in all patients. ZDV was cleared from the CSF with a mean t 1/2 of 187.6 +/- 69.3 minutes. Mean Cmax in the CSF was 1.3 +/- 1.2 micromol/l (17% of that of plasma), and mean area under the concentration time curve (AUC) was 358 +/- 200 micromol x minutes/l (75% of that of plasma). There was a significant correlation between plasma and CSF for Cmax (r = 0.88, p = .009) and AUC (r = 0.89, p = .014). Calculated trough levels in CSF for a 12-hour dosing interval were 0.090 +/- 0.065 micromol/l and thus about twice the 50% inhibitory concentration (IC50) of susceptible HIV strains. The CSF-plasma ratio of ZDV increased in a nearly linear fashion with time after drug administration. Thus, ZDV has a distinct pharmacokinetic profile in CSF compared with other compartments of the body.