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 (C(max)) was 0.135 ± 0.06 mmol/L and mean trough 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 absorbed from the gastrointestinal tract, with a t(max) 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 viva inhibition of HIV-1.
| Original language | English |
|---|---|
| Pages (from-to) | 117-121 |
| Number of pages | 5 |
| Journal | Journal of Clinical Pharmacology |
| Volume | 36 |
| Issue number | 2 |
| Publication status | Published - Feb 1996 |
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ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Pharmacokinetics of hydroxyurea in patients infected with human immunodeficiency virus type I. / Viliani, Paola; Maserati, Renato; Regazzi, Mario B.; Giacchino, Roberto; Lori, Franco.
In: Journal of Clinical Pharmacology, Vol. 36, No. 2, 02.1996, p. 117-121.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics of hydroxyurea in patients infected with human immunodeficiency virus type I
AU - Viliani, Paola
AU - Maserati, Renato
AU - Regazzi, Mario B.
AU - Giacchino, Roberto
AU - Lori, Franco
PY - 1996/2
Y1 - 1996/2
N2 - 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 (C(max)) was 0.135 ± 0.06 mmol/L and mean trough 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 absorbed from the gastrointestinal tract, with a t(max) 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 viva inhibition of HIV-1.
AB - 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 (C(max)) was 0.135 ± 0.06 mmol/L and mean trough 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 absorbed from the gastrointestinal tract, with a t(max) 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 viva inhibition of HIV-1.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029923839&partnerID=8YFLogxK
M3 - Article
VL - 36
SP - 117
EP - 121
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
SN - 0091-2700
IS - 2
ER -