title: Pharmacokinetics of hydroxyurea in patients infected with human immunodeficiency virus type I.
abstract: In a prospective, randomized, controlled, three-arm study, the pharmacokinetics of hydroxyurea administered as an antiviral agent in patients infected with human immunodeficiency virus type 1 (HIV-1) were evaluated. The three arms of the study consisted of azidothymidine (AZT) 250 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 venipunctures for pharmacokinetic analysis. Sample collection was performed at steady-state conditions and serum concentration-time data for hydroxyurea were fitted using a one-compartment model. Mean (+/- standard deviation) peak concentration (Cmax) was 0.135 +/- 0.06 mmol/L and mean trough level (Cmin) 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 (t1/2) was 2.5 +/- 0.5 hours. Hydroxyurea given orally to patients infected with HIV-1 was well absorbed from the gastrointestinal tract, with a tmax of 0.85 to 0.96 hours 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 show that hydroxyurea given at a dosage of 500 mg twice daily is sufficient to yield serum concentrations potentially useful for in vivo inhibition of HIV-1.
authors.affiliation: Department of Pharmacology, IRCCS, Policlinico S. Matteo, Pavia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Villani
authors.forename: R
authors.initials: R
authors.lastname: Maserati
authors.forename: M B
authors.initials: MB
authors.lastname: Regazzi
authors.forename: R
authors.initials: R
authors.lastname: Giacchino
authors.forename: F
authors.initials: F
authors.lastname: Lori
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D006918:Hydroxyurea / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D015215:Zidovudine; D006918:Hydroxyurea