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Keywords:

  • drug interaction;
  • pharmacokinetic;
  • protease inhibitors

Aims

To evaluate the interindividual variability in the plasma concentrations of lopinavir in the context of routine monitoring with or without treatment with a non-nucleoside reverse transcriptase inhibitor and to assess the interaction between the coformulation of lopinavir/ritonavir and efavirenz or nevirapine.

Methods

Plasma trough and peak concentrations (Ctrough, Cmax) of lopinavir from 182 HIV-1-infected patients were analysed by high-performace liquid chromatography. Three lopinavir/ritonavir regimens were assessed, namely (A) 400 mg lopinavir/100 mg ritonavir twice daily given alone (n = 125), (B) 400/100 mg twice daily together with a non-nucleoside reverse transcriptase inhibitor (n = 25), and (C) 533/133 mg twice daily together with a non-nucleoside reverse transcriptase inhibitor (n = 32).

Results

Median (ng ml−1) Ctrough and Cmax lopinavir (interquartile range, CV) were: (A) 4852 (3198–6891, 56%) and 8501 (6333–11 584, 41%), (B) 2979 (1704–5186, 74%) and 5612 (3362–11 704, 76%) and (C) 5082 (2696–7226, 74%) and 9757 (4883–12 963, 60%). Median Ctrough of lopinavir was lower in patients taking both efavirenz [P = 0.01, 95% confidence interval (CI) for difference between medians 343, 2713] and nevirapine (P = 0.019, 95% CI for difference between medians 354, 3681) compared with those taking lopinavir/ritonavir alone. A higher interindividual variability was observed when lopinavir/ritonavir was given with a non-nucleoside reverse transcriptase inhibitor. The risk of achieving a ‘suboptimal’Ctrough of lopinavir (below a threshold of 3000 ng ml−1) was statistically higher in patients treated with a non-nucleoside reverse transcriptase inhibitor (P < 0.001, 95% CI for difference between percentages 8.8, 43.1%) compared with those receiving lopinavir/ritonavir alone.

Conclusions

Our results confirmed the interaction between lopinavir and efavirenz, and also demonstrated a significant interaction between the former drug and nevirapine, resulting in lower Ctrough of lopinavir. The wide interpatient variability in this interaction suggests that therapeutic drug monitoring may be useful in optimizing the dose of lopinavir.