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Abstract
Dose changes, intrapatient variability, and exposure to lopinavir(LPV) - Implications for the use of therapeutic drug monitoring in the clinical setting
C S Alexander, J S Montaner, J J Asselin, L S Ting, K McNabb, M Harris, S Guillemi, P R Harrigan
B.C. Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
Background: Dose changes based on the results of therapeutic drug monitoring (TDM) are only beneficial if the change alters exposure. Here we examine the changes in LPV plasma concentrations after changes in LPV/ritonavir (RTV) dose observed in a clinical setting for patients receiving twice-daily LPV/RTV.
Methods: The study included 32 patients who received TDM tests both before and after changes of their LPV/RTV dose with no changes in other PIs or NNRTIs, and 12 patients with > 2 tests while on the same regimen (N = 44). Timed blood samples were drawn within a 12 hour dosing period after >2 weeks on a stable regimen. Plasma LPV concentrations were determined by a validated assay using HPLC/MS/MS. Linear mixed effects models were used to investigate the effect of dose change on timed concentrations and partial area under the plasma concentration curve (AUC).
Results: Plasma concentrations and partial AUCs were significantly associated with dose (p < 0.001 for both). In particular, an increase from 400/100 to 533/133 mg results in a median increase in timed concentration and AUC of 1.4-fold and 1.5-fold, respectively. Notably, 28% of patients showed a clinically insignificant (<10%) increase in AUC with the addition of a single 133/33 mg LPV/RTV dose to their regimen, including 4 patients who exhibited drop in exposure at the higher dose. This may be due in part to a large intrapatient variability with the 95% confidence intervals for day-to-day observations being 40% - 248% and 51% - 197% for trough and AUC respectively.
Conclusions: Altering LPV/RTV dose based on plasma drug level data can improve patient exposures; however, the large intrapatient variability complicates interpretation of the results. Re-evaluation of exposure is recommended after LPV/RTV dose changes.
The XV International AIDS Conference
Abstract no.
TuPeB4642
Suggested Citation
" C S Alexander, et al.
Dose changes, intrapatient variability, and exposure to lopinavir(LPV) - Implications for the use of therapeutic drug monitoring in the clinical setting
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Poster Exhibition:
The XV International AIDS Conference:
Abstract no.
TuPeB4642"
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