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Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.

Publication ,  Journal Article
Heald, AE; Hsyu, PH; Yuen, GJ; Robinson, P; Mydlow, P; Bartlett, JA
Published in: Antimicrob Agents Chemother
June 1996

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

June 1996

Volume

40

Issue

6

Start / End Page

1514 / 1519

Location

United States

Related Subject Headings

  • Middle Aged
  • Microbiology
  • Metabolic Clearance Rate
  • Male
  • Lamivudine
  • Kidney Diseases
  • Humans
  • Half-Life
  • Female
  • Antiviral Agents
 

Citation

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Heald, A. E., Hsyu, P. H., Yuen, G. J., Robinson, P., Mydlow, P., & Bartlett, J. A. (1996). Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother, 40(6), 1514–1519. https://doi.org/10.1128/AAC.40.6.1514
Heald, A. E., P. H. Hsyu, G. J. Yuen, P. Robinson, P. Mydlow, and J. A. Bartlett. “Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.Antimicrob Agents Chemother 40, no. 6 (June 1996): 1514–19. https://doi.org/10.1128/AAC.40.6.1514.
Heald AE, Hsyu PH, Yuen GJ, Robinson P, Mydlow P, Bartlett JA. Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother. 1996 Jun;40(6):1514–9.
Heald, A. E., et al. “Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.Antimicrob Agents Chemother, vol. 40, no. 6, June 1996, pp. 1514–19. Pubmed, doi:10.1128/AAC.40.6.1514.
Heald AE, Hsyu PH, Yuen GJ, Robinson P, Mydlow P, Bartlett JA. Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother. 1996 Jun;40(6):1514–1519.

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

June 1996

Volume

40

Issue

6

Start / End Page

1514 / 1519

Location

United States

Related Subject Headings

  • Middle Aged
  • Microbiology
  • Metabolic Clearance Rate
  • Male
  • Lamivudine
  • Kidney Diseases
  • Humans
  • Half-Life
  • Female
  • Antiviral Agents