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Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non-parametric approach

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aims

Nevirapine is the first non-nucleoside reverse-transcriptase inhibitor approved and is widely used in combination therapy to treat HIV-1 infection. The pharmacokinetics of nevirapine was extensively studied in various populations with a parametric approach. Hence, this study was aimed to determine population pharmacokinetic parameters in Malaysian HIV-infected patients with a non-parametric approach which allows detection of outliers or non-normal distribution contrary to the parametric approach.

Methods

Nevirapine population pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112 patients were included in the model building and validation analysis. Evaluation of the model was based on a visual inspection of observed versus predicted (population and individual) concentrations and plots weighted residual error versus concentrations. Accuracy and robustness of the model were evaluated by visual predictive check (VPC). The median parameters’ estimates obtained from the final model were used to predict individual nevirapine plasma area-under-curve (AUC) in the validation dataset. The Bland-Altman plot was used to compare the AUC predicted with trapezoidal AUC.

Results

The median nevirapine clearance was of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one-compartmental with first-order absorption model and a lag-time. Weighted residuals for the model selected were homogenously distributed over the concentration and time range. The developed model adequately estimated AUC.

Conclusions

In conclusion, a model to describe the pharmacokinetics of nevirapine was developed. The developed model adequately describes nevirapine population pharmacokinetics in HIV-infected patients in Malaysia.

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Acknowledgments

This work was financially supported by Universiti Sains Malaysia RU Grant (grant no. 1001/PSK/8620015). The first author was supported by Malaysia Ministry of Health Hadiah Latihan Persekutuan. The authors thank Dr Mahiran Mustafa (HRPZ II), Dr Ahmad Kashfi Ab Rahman (HSNZ) and Dr Low Lee Lee (HSB) for their co-operation in conducting the research. The authors also acknowledge staff members of INFORMM (USM), Kelantan, nurses and pharmacists of Infectious Disease Clinics of HRPZ II, HSNZ and HSB, Malaysia for their support and help.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16100, Kubang Kerian, Kelantan, Malaysia

    Suzana Mustafa, Wan Nazirah Wan Yusuf & Norul Badriah Hassan

  2. Hospital Raja Perempuan Zainab II, Kelantan, Malaysia

    Suzana Mustafa

  3. INSERM UMR 850, Université de Limoges CHU, Limoges, France

    Jean Baptiste Woillard

  4. Institutes for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang, Malaysia

    Tan Soo Choon

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  1. Suzana Mustafa
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  2. Wan Nazirah Wan Yusuf
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  3. Jean Baptiste Woillard
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  4. Tan Soo Choon
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  5. Norul Badriah Hassan
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Correspondence to Suzana Mustafa.

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Mustafa, S., Yusuf, W.N.W., Woillard, J.B. et al. Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non-parametric approach. Eur J Clin Pharmacol 72, 831–838 (2016). https://doi.org/10.1007/s00228-016-2049-6

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  • DOI: https://doi.org/10.1007/s00228-016-2049-6

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