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The relation between total and free plasma concentrations of nucleoside reverse transcriptase inhibitors in HIV‐infected children
Author(s) -
Rakhmani. Y.,
Anker J. N.,
Sever J.,
Spiegel H.,
Soldin S.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.273
Subject(s) - stavudine , lamivudine , zidovudine , nucleoside , reverse transcriptase inhibitor , nucleoside reverse transcriptase inhibitor , human immunodeficiency virus (hiv) , pharmacology , reverse transcriptase , pharmacokinetics , plasma concentration , medicine , plasma levels , virology , chemistry , antiretroviral therapy , virus , viral load , biochemistry , viral disease , rna , hepatitis b virus , gene
Purpose A significant relationship between the intracellular concentrations (ICC) of nucleoside reverse transcriptase inhibitors (NRTIs) metabolites and outcome parameters in HIV infection exists. Variability in free plasma concentrations of NRTIs may contribute to the variability in ICC of their triphosphate metabolites. To date no studies have investigated the relation between total and free plasma concentration of NRTIs. Our purpose was to determine the total and free concentrations of lamivudine (3TC), stavudine (d4T) and zidovudine (AZT) in plasma in HIV‐infected children. Methods 22 pediatric patients (median age 8.9 years) were enrolled in the study. Unbound 3Tc, d4T, and AZT were separated by ultrafiltration. The drug plasma concentrations were determined by tandem‐MS using Sciex APT‐2000. Routine statistical methods were used. Results There was a highly significant relation between total and free plasma concentrations for all three NRTIs with a r‐value of 0.995 for 3TC (3TC freepl =0.95×3TC totalpl ‐36.51, p<0.0001), a r‐value of 0.924 for d4T (d4T freepl = 0.65×d4T totalpl ‐3.61, p<0.0001), and a r‐ value of 0.907 for AZT (AZT freepl = 0.14×AZT totalpl +27.3, p<0.002). Conclusion This pilot study showed a significant linear correlation between total and free plasma concentration of 3TC, d4T and AZT in pediatric HIV‐infected children. Future studies need to investigate the relation between free plasma concentrations of NRTIs and ICC of their active metabolites. Clinical Pharmacology & Therapeutics (2004) 75 , P72–P72; doi: 10.1016/j.clpt.2003.11.273