Pharmacokinetics of new 625mg nelfinavir formulation during pregnancy and postpartum

Jennifer S. Read, B. M. Best, A. M. Stek, Chengcheng Hu, E. V. Capparelli, D. T. Holland, S. K. Burchett, M. E. Smith, E. C. Sheeran, W. T. Shearer, I. Febo, M. Mirochnick

Research output: Contribution to journalArticle

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Abstract

Objectives: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. Methods: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC0-12) was ≥ 10th percentile NFV AUC0-12 in non-pregnant historical controls (18.5 μgh/mL). Results: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (Cmax), 12-h post-dose concentration (C12) and AUC0-12 were significantly lower during the third trimester compared to postpartum (P ≤ 0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC0-12 and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P < 0.01). The NFV AUC0-12 exceeded the AUC0-12 target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (Cmin) was above the suggested minimum trough concentration (0.8 μg/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was < 400HIV-1 RNAcopies/mL in 81% of patients at delivery. Conclusions: These results suggest that higher doses of NFV should be considered during pregnancy.

Original languageEnglish (US)
Pages (from-to)875-882
Number of pages8
JournalHIV Medicine
Volume9
Issue number10
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Nelfinavir
Postpartum Period
Pharmacokinetics
Pregnancy
Third Pregnancy Trimester
Tablets
Second Pregnancy Trimester
Viral Load
Hydroxyl Radical
Area Under Curve
HIV-1
Pregnant Women

Keywords

  • HIV
  • Nelfinavir
  • Pharmacokinetics
  • Pregnancy

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Health Policy

Cite this

Read, J. S., Best, B. M., Stek, A. M., Hu, C., Capparelli, E. V., Holland, D. T., ... Mirochnick, M. (2008). Pharmacokinetics of new 625mg nelfinavir formulation during pregnancy and postpartum. HIV Medicine, 9(10), 875-882. https://doi.org/10.1111/j.1468-1293.2008.00640.x

Pharmacokinetics of new 625mg nelfinavir formulation during pregnancy and postpartum. / Read, Jennifer S.; Best, B. M.; Stek, A. M.; Hu, Chengcheng; Capparelli, E. V.; Holland, D. T.; Burchett, S. K.; Smith, M. E.; Sheeran, E. C.; Shearer, W. T.; Febo, I.; Mirochnick, M.

In: HIV Medicine, Vol. 9, No. 10, 11.2008, p. 875-882.

Research output: Contribution to journalArticle

Read, JS, Best, BM, Stek, AM, Hu, C, Capparelli, EV, Holland, DT, Burchett, SK, Smith, ME, Sheeran, EC, Shearer, WT, Febo, I & Mirochnick, M 2008, 'Pharmacokinetics of new 625mg nelfinavir formulation during pregnancy and postpartum', HIV Medicine, vol. 9, no. 10, pp. 875-882. https://doi.org/10.1111/j.1468-1293.2008.00640.x
Read, Jennifer S. ; Best, B. M. ; Stek, A. M. ; Hu, Chengcheng ; Capparelli, E. V. ; Holland, D. T. ; Burchett, S. K. ; Smith, M. E. ; Sheeran, E. C. ; Shearer, W. T. ; Febo, I. ; Mirochnick, M. / Pharmacokinetics of new 625mg nelfinavir formulation during pregnancy and postpartum. In: HIV Medicine. 2008 ; Vol. 9, No. 10. pp. 875-882.
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abstract = "Objectives: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. Methods: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC0-12) was ≥ 10th percentile NFV AUC0-12 in non-pregnant historical controls (18.5 μgh/mL). Results: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (Cmax), 12-h post-dose concentration (C12) and AUC0-12 were significantly lower during the third trimester compared to postpartum (P ≤ 0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC0-12 and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P < 0.01). The NFV AUC0-12 exceeded the AUC0-12 target for 15/27 (56{\%}) and 21/22 (95{\%}) of third trimester and postpartum patients, respectively. The minimum concentration (Cmin) was above the suggested minimum trough concentration (0.8 μg/mL) in 15{\%} (third trimester) and 18{\%} (postpartum). The plasma viral load was < 400HIV-1 RNAcopies/mL in 81{\%} of patients at delivery. Conclusions: These results suggest that higher doses of NFV should be considered during pregnancy.",
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AU - Read, Jennifer S.

AU - Best, B. M.

AU - Stek, A. M.

AU - Hu, Chengcheng

AU - Capparelli, E. V.

AU - Holland, D. T.

AU - Burchett, S. K.

AU - Smith, M. E.

AU - Sheeran, E. C.

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AU - Febo, I.

AU - Mirochnick, M.

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N2 - Objectives: Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. Methods: The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC0-12) was ≥ 10th percentile NFV AUC0-12 in non-pregnant historical controls (18.5 μgh/mL). Results: Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (Cmax), 12-h post-dose concentration (C12) and AUC0-12 were significantly lower during the third trimester compared to postpartum (P ≤ 0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC0-12 and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P < 0.01). The NFV AUC0-12 exceeded the AUC0-12 target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (Cmin) was above the suggested minimum trough concentration (0.8 μg/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was < 400HIV-1 RNAcopies/mL in 81% of patients at delivery. Conclusions: These results suggest that higher doses of NFV should be considered during pregnancy.

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