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Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii.

Publication ,  Journal Article
Jacobson, JM; Davidian, M; Rainey, PM; Hafner, R; Raasch, RH; Luft, BJ
Published in: Antimicrob Agents Chemother
June 1996

Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102). Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose. Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 micrograms.h/ml; halflife, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection. Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

June 1996

Volume

40

Issue

6

Start / End Page

1360 / 1365

Location

United States

Related Subject Headings

  • Zidovudine
  • Toxoplasmosis
  • Pyrimethamine
  • Microbiology
  • Male
  • Humans
  • Half-Life
  • HIV Infections
  • Drug Interactions
  • AIDS-Related Opportunistic Infections
 

Citation

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Jacobson, J. M., Davidian, M., Rainey, P. M., Hafner, R., Raasch, R. H., & Luft, B. J. (1996). Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii. Antimicrob Agents Chemother, 40(6), 1360–1365. https://doi.org/10.1128/AAC.40.6.1360
Jacobson, J. M., M. Davidian, P. M. Rainey, R. Hafner, R. H. Raasch, and B. J. Luft. “Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii.Antimicrob Agents Chemother 40, no. 6 (June 1996): 1360–65. https://doi.org/10.1128/AAC.40.6.1360.
Jacobson JM, Davidian M, Rainey PM, Hafner R, Raasch RH, Luft BJ. Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii. Antimicrob Agents Chemother. 1996 Jun;40(6):1360–5.
Jacobson, J. M., et al. “Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii.Antimicrob Agents Chemother, vol. 40, no. 6, June 1996, pp. 1360–65. Pubmed, doi:10.1128/AAC.40.6.1360.
Jacobson JM, Davidian M, Rainey PM, Hafner R, Raasch RH, Luft BJ. Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii. Antimicrob Agents Chemother. 1996 Jun;40(6):1360–1365.

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

June 1996

Volume

40

Issue

6

Start / End Page

1360 / 1365

Location

United States

Related Subject Headings

  • Zidovudine
  • Toxoplasmosis
  • Pyrimethamine
  • Microbiology
  • Male
  • Humans
  • Half-Life
  • HIV Infections
  • Drug Interactions
  • AIDS-Related Opportunistic Infections