PHARMACOKINETICS OF HYDROXYUREA IN PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I

In a prospective, randomized, controlled, three-arm study, the pharmac okinetics of hydroxyurea administered as an antiviral agent in patient s infected with human immunodeficiency virus type 1 (HIV-1) were evalu ated. The three arms of the study consisted of azidothymidine (AZT) 25 0 mg twice daily, hydroxyurea 500 mg twice daily, or a combination of the two. Nine patients receiving hydroxyurea in monotherapy (n = 4) or in combination with AZT (n = 5) agreed to undergo multiple venipunctu res for pharmacokinetic analysis. Sample collection was performed at s teady-state conditions and serum concentration-time data for hydroxyur ea were fitted using a one-compartment model. Mean (+/- standard devia tion) peak concentration (C-max) was 0.135 +/- 0.06 mmol/L and mean tr ough level (C-min) was 0.0085 +/- 0.003 mmol/L. Mean concentration at steady state was 0.045 +/- 0.006 mmol/L. Apparent clearance (Cl/F) was 0.18 +/- 0.005 L/hr/kg, and half-life (t(1/2)) was 2.5 +/- 0.5 hours, Hydroxyurea given orally to patients infected with HIV-1 was well abs orbed from the gastrointestinal tract, with a t(max) of 0.85 to 0.96 h ours after ingestion. Serum levels of hydroxyurea ranged from 0.01 to 0.13 mmol/L. These values are similar to the concentrations (between 0 .01 and 0.1 mmol/L) demonstrated to inhibit HIV-1 in vitro. Our data s how that hydroxyurea given at a dosage of 500 mg twice daily is suffic ient to yield serum concentrations potentially useful for in vivo inhi bition of HIV-1.