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Risk of undertreatment with the standard abacavir 300 mg dose
Author(s) -
Jullien V.,
Urien S.,
Dimet J.,
Rey E.,
Dupin N.,
Salmon D.,
Pons G.,
Treluyer J.
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.2003.11.058
Subject(s) - abacavir , pharmacokinetics , volume of distribution , elimination rate constant , pharmacology , population , plasma concentration , plasma clearance , distribution (mathematics) , chemistry , medicine , mathematics , human immunodeficiency virus (hiv) , immunology , antiretroviral therapy , mathematical analysis , environmental health , viral load
Purpose To study the relevance of the current 300 mg B.I.D. abacavir dose for H.I.V.‐infected adults. Methods Abacavir plasma concentrations were obtained from therapeutic drug monitoring results. Population pharmacokinetic analysis was performed using a nonlinear mixed effects modeling method. Results Abacavir concentration‐time profiles were best described by a one‐compartment open‐model with linear absorption and elimination. Typical values of absorption rate constant, apparent distribution volume and apparent plasma clearance (CL/F) were 3.3 h −1 , 98 L and 48 L/h respectively. CL/F was positively related to BW. A risk of undertreatment as a function of BW was identified as the percentage of patients reaching the area under the curve value providing the optimal antiviral efficacy decreased from 94 to 22 % when BW increased from 36 to 102 kg. Conclusion This study identified BW as a major determinant of abacavir clearance. These results suggest the administration of larger doses to high BW patients. Clinical Pharmacology & Therapeutics (2004) 75 , P16–P16; doi: 10.1016/j.clpt.2003.11.058