Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosingCitation formats

  • External authors:
  • Laura Dickinson
  • Marta Boffito
  • Saye H. Khoo
  • Malte Schutz
  • Anton L. Pozniak
  • David J. Back

Standard

Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing. / Dickinson, Laura; Boffito, Marta; Khoo, Saye H.; Schutz, Malte; Aarons, Leon J.; Pozniak, Anton L.; Back, David J.

In: Journal of Antimicrobial Chemotherapy, Vol. 62, No. 1, 07.2008, p. 161-167.

Research output: Contribution to journalArticle

Harvard

Dickinson, L, Boffito, M, Khoo, SH, Schutz, M, Aarons, LJ, Pozniak, AL & Back, DJ 2008, 'Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing', Journal of Antimicrobial Chemotherapy, vol. 62, no. 1, pp. 161-167. https://doi.org/10.1093/jac/dkn187

APA

Dickinson, L., Boffito, M., Khoo, S. H., Schutz, M., Aarons, L. J., Pozniak, A. L., & Back, D. J. (2008). Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing. Journal of Antimicrobial Chemotherapy, 62(1), 161-167. https://doi.org/10.1093/jac/dkn187

Vancouver

Dickinson L, Boffito M, Khoo SH, Schutz M, Aarons LJ, Pozniak AL et al. Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing. Journal of Antimicrobial Chemotherapy. 2008 Jul;62(1):161-167. https://doi.org/10.1093/jac/dkn187

Author

Dickinson, Laura ; Boffito, Marta ; Khoo, Saye H. ; Schutz, Malte ; Aarons, Leon J. ; Pozniak, Anton L. ; Back, David J. / Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing. In: Journal of Antimicrobial Chemotherapy. 2008 ; Vol. 62, No. 1. pp. 161-167.

Bibtex

@article{13d961b9874943e591a50219b3c8635c,
title = "Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing",
abstract = "Objectives: One potential concern of once-daily protease inhibitor administration is low trough concentrations and ultimately the 'forgiveness' or robustness in comparison with the originally licensed twice-daily dose. To give an estimation of 'forgiveness', we determined the length of time plasma drug concentrations were below target in HIV-infected patients receiving saquinavir/ritonavir regimens. Methods: Seventy-seven pharmacokinetic profiles (saquinavir/ritonavir 1000/100 mg twice daily, n = 34; 1600/100 mg once daily, n = 26; 2000/100 mg once daily, n = 17) from five studies were combined, presented as twice- and once-daily percentiles (P10 - P90) and compared. At percentiles where trough concentrations fell below the alleged minimum effective concentration (MEC; 100 ng/mL), the length of time below MEC was determined. Results: Saquinavir concentrations were below MEC at P10 for 0.7 h for twice-daily saquinavir/ritonavir when compared with 8.6 and 6.6 h for 1600/100 and 2000/100 mg once daily, respectively. At P25, 1600/100 mg once daily produced suboptimal concentrations for 5.5 h in contrast to 0.5 h for 2000/100 mg once daily. Conclusions: Here, we provide substantive data that indicate once-daily saquinavir, in particular 1600/100 mg, is not as robust as the twice-daily regimen based on a population of UK patients; this raises concern over late or missed doses. However, pharmacokinetic data can only ever be a guide to the impact on long-term efficacy. {\circledC} The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.",
keywords = "HIV, Once daily, Pharmacokinetics, Robustness",
author = "Laura Dickinson and Marta Boffito and Khoo, {Saye H.} and Malte Schutz and Aarons, {Leon J.} and Pozniak, {Anton L.} and Back, {David J.}",
year = "2008",
month = "7",
doi = "10.1093/jac/dkn187",
language = "English",
volume = "62",
pages = "161--167",
journal = "The Journal of antimicrobial chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing

AU - Dickinson, Laura

AU - Boffito, Marta

AU - Khoo, Saye H.

AU - Schutz, Malte

AU - Aarons, Leon J.

AU - Pozniak, Anton L.

AU - Back, David J.

PY - 2008/7

Y1 - 2008/7

N2 - Objectives: One potential concern of once-daily protease inhibitor administration is low trough concentrations and ultimately the 'forgiveness' or robustness in comparison with the originally licensed twice-daily dose. To give an estimation of 'forgiveness', we determined the length of time plasma drug concentrations were below target in HIV-infected patients receiving saquinavir/ritonavir regimens. Methods: Seventy-seven pharmacokinetic profiles (saquinavir/ritonavir 1000/100 mg twice daily, n = 34; 1600/100 mg once daily, n = 26; 2000/100 mg once daily, n = 17) from five studies were combined, presented as twice- and once-daily percentiles (P10 - P90) and compared. At percentiles where trough concentrations fell below the alleged minimum effective concentration (MEC; 100 ng/mL), the length of time below MEC was determined. Results: Saquinavir concentrations were below MEC at P10 for 0.7 h for twice-daily saquinavir/ritonavir when compared with 8.6 and 6.6 h for 1600/100 and 2000/100 mg once daily, respectively. At P25, 1600/100 mg once daily produced suboptimal concentrations for 5.5 h in contrast to 0.5 h for 2000/100 mg once daily. Conclusions: Here, we provide substantive data that indicate once-daily saquinavir, in particular 1600/100 mg, is not as robust as the twice-daily regimen based on a population of UK patients; this raises concern over late or missed doses. However, pharmacokinetic data can only ever be a guide to the impact on long-term efficacy. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

AB - Objectives: One potential concern of once-daily protease inhibitor administration is low trough concentrations and ultimately the 'forgiveness' or robustness in comparison with the originally licensed twice-daily dose. To give an estimation of 'forgiveness', we determined the length of time plasma drug concentrations were below target in HIV-infected patients receiving saquinavir/ritonavir regimens. Methods: Seventy-seven pharmacokinetic profiles (saquinavir/ritonavir 1000/100 mg twice daily, n = 34; 1600/100 mg once daily, n = 26; 2000/100 mg once daily, n = 17) from five studies were combined, presented as twice- and once-daily percentiles (P10 - P90) and compared. At percentiles where trough concentrations fell below the alleged minimum effective concentration (MEC; 100 ng/mL), the length of time below MEC was determined. Results: Saquinavir concentrations were below MEC at P10 for 0.7 h for twice-daily saquinavir/ritonavir when compared with 8.6 and 6.6 h for 1600/100 and 2000/100 mg once daily, respectively. At P25, 1600/100 mg once daily produced suboptimal concentrations for 5.5 h in contrast to 0.5 h for 2000/100 mg once daily. Conclusions: Here, we provide substantive data that indicate once-daily saquinavir, in particular 1600/100 mg, is not as robust as the twice-daily regimen based on a population of UK patients; this raises concern over late or missed doses. However, pharmacokinetic data can only ever be a guide to the impact on long-term efficacy. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

KW - HIV

KW - Once daily

KW - Pharmacokinetics

KW - Robustness

U2 - 10.1093/jac/dkn187

DO - 10.1093/jac/dkn187

M3 - Article

VL - 62

SP - 161

EP - 167

JO - The Journal of antimicrobial chemotherapy

JF - The Journal of antimicrobial chemotherapy

SN - 0305-7453

IS - 1

ER -