Pharmacokinetic strategies for concentration-targeted therapy with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV)

C. V. Fletcher, T. N. Kakuda, L. M. Page, E. P. Acosta, R. C. Brundage, P. L. Anderson, K. Henry, T. Schacker

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Concentration-targeted (C) strategies may reduce pharmacologic variability, which has been suggested as one factor in the heterogeneity in antiretroviral response. Methods: Antiretroviral-naive persons are randomized to standard dose therapy (S) with ZDV, 3TC, and IDV, or a C regimen. Targets are: ZDV, Css≥0.19 mg/L; 3TC, Css≥0.44 mg/L; and IDV, C8h≥0.15 mg/L. Serial concentrations are measured after 2 wks and parameters determined with Bayesian-estimation; dose adjustments are performed in C recipients to achieve desired targets. Single timed concentrations are measured every 4 weeks and compared with predicted allowing for possible analytical and dose-sample timing errors. Results: Data are available for 24 patients, 13 S and 11 C. Oral clearance of ZDV, 3TC, and IDV at wk 2 was not different between S vs C; overall mean values (L/h/kg) were: ZDV, 2.15±1.1; 3TC, 0.36±0.09; IDV, 0.74±0.29. After dose adjustments, average values (mg/L) achieved with C were: ZDV, Css=0.21; 3TC, Css=0.46; and IDV, C8h=0.17. C therapy reduced variability in ZDV Css by 54%, and 3TC by 24%; IDV C8h were higher in C vs S (0.17 vs 0.06 mg/L, p=0.01). In 10 patients with 6 mo of C therapy, the median % of samples ≥ target was: ZDV, 100%; 3TC, 100%; IDV, 83%. Conclusions: C therapy with ZDV, 3TC, and IDV is feasible and reduces inter-patient variability in systemic exposure.

Original languageEnglish (US)
Number of pages1
JournalClinical Pharmacology and Therapeutics
Volume65
Issue number2
DOIs
StatePublished - Jan 1 1999

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Indinavir
Lamivudine
Zidovudine
Pharmacokinetics
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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Pharmacokinetic strategies for concentration-targeted therapy with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). / Fletcher, C. V.; Kakuda, T. N.; Page, L. M.; Acosta, E. P.; Brundage, R. C.; Anderson, P. L.; Henry, K.; Schacker, T.

In: Clinical Pharmacology and Therapeutics, Vol. 65, No. 2, 01.01.1999.

Research output: Contribution to journalArticle

Fletcher, C. V. ; Kakuda, T. N. ; Page, L. M. ; Acosta, E. P. ; Brundage, R. C. ; Anderson, P. L. ; Henry, K. ; Schacker, T. / Pharmacokinetic strategies for concentration-targeted therapy with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). In: Clinical Pharmacology and Therapeutics. 1999 ; Vol. 65, No. 2.
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abstract = "Concentration-targeted (C) strategies may reduce pharmacologic variability, which has been suggested as one factor in the heterogeneity in antiretroviral response. Methods: Antiretroviral-naive persons are randomized to standard dose therapy (S) with ZDV, 3TC, and IDV, or a C regimen. Targets are: ZDV, Css≥0.19 mg/L; 3TC, Css≥0.44 mg/L; and IDV, C8h≥0.15 mg/L. Serial concentrations are measured after 2 wks and parameters determined with Bayesian-estimation; dose adjustments are performed in C recipients to achieve desired targets. Single timed concentrations are measured every 4 weeks and compared with predicted allowing for possible analytical and dose-sample timing errors. Results: Data are available for 24 patients, 13 S and 11 C. Oral clearance of ZDV, 3TC, and IDV at wk 2 was not different between S vs C; overall mean values (L/h/kg) were: ZDV, 2.15±1.1; 3TC, 0.36±0.09; IDV, 0.74±0.29. After dose adjustments, average values (mg/L) achieved with C were: ZDV, Css=0.21; 3TC, Css=0.46; and IDV, C8h=0.17. C therapy reduced variability in ZDV Css by 54{\%}, and 3TC by 24{\%}; IDV C8h were higher in C vs S (0.17 vs 0.06 mg/L, p=0.01). In 10 patients with 6 mo of C therapy, the median {\%} of samples ≥ target was: ZDV, 100{\%}; 3TC, 100{\%}; IDV, 83{\%}. Conclusions: C therapy with ZDV, 3TC, and IDV is feasible and reduces inter-patient variability in systemic exposure.",
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AU - Fletcher, C. V.

AU - Kakuda, T. N.

AU - Page, L. M.

AU - Acosta, E. P.

AU - Brundage, R. C.

AU - Anderson, P. L.

AU - Henry, K.

AU - Schacker, T.

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