Pharmacokinetic bioequivalence of enfuvirtide using a needle-free device versus standard needle administration

Pharmacotherapy. 2006 Dec;26(12):1679-86. doi: 10.1592/phco.26.12.1679.

Abstract

Study objectives: To compare the relative bioavailability of enfuvirtide, a human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, injected with the Biojector 2000 (B2000) needle-free device versus a 27-gauge half-inch needle-syringe; and to assess safety, tolerability, and patient preference for the two devices.

Design: Open-label, randomized, two-period crossover bioequivalence evaluation.

Setting: Clinical research center.

Patients: Twenty-seven adults with HIV-1 viral loads below 1000 copies/ml.

Intervention: Each patient received enfuvirtide 90 mg subcutaneously with the B2000 and with the needle-syringe, with a 1-week washout between treatments.

Measurements and main results: Twenty-six and 27 patients were included in the bioequivalence and safety analyses, respectively. Plasma enfuvirtide concentrations were measured at baseline and at several intervals after each injection. The B2000:needle-syringe ratios of maximum concentration (C(max)), area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)), and AUC from time zero to tau (dosing interval) (AUC(0-tau)) served as criteria for bioequivalence determination. The two drug delivery systems were considered bioequivalent if the 90% confidence intervals (CIs) for the ratios were within 0.8-1.25. Safety and tolerability were evaluated based on documentation of adverse events, graded laboratory toxicities, and local injection-site reactions. Patient surveys provided feedback on device preference. Ratios of C(max), AUC(0-infinity), and AUC(0-tau) were 0.95 (90% CI 0.84-1.09), 0.99 (90% CI 0.93-1.05), and 0.99 (90% CI 0.93-1.05), respectively. The frequency of injection-site reactions was low, and severity was generally mild for both devices. Survey results showed 18 patients (69%) had a positive overall impression of the B2000 and 14 (54%) felt safer injecting with this device. Overall, 17 patients (65%) preferred the B2000 over the needle-syringe.

Conclusion: Bioavailability of enfuvirtide with the B2000 and needle-syringe was equivalent based on C(max), AUC(0-tau), and AUC(0-infinity). Safety profiles and injection-site reactions were comparable between the devices, but patients preferred the B2000. Delivery of enfuvirtide with the B2000 is a feasible alternative to standard needle administration and warrants further evaluation.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Cross-Over Studies
  • Enfuvirtide
  • Female
  • HIV Envelope Protein gp41 / administration & dosage
  • HIV Envelope Protein gp41 / therapeutic use*
  • HIV Fusion Inhibitors / administration & dosage
  • HIV Fusion Inhibitors / pharmacokinetics*
  • HIV Fusion Inhibitors / therapeutic use*
  • HIV Infections / drug therapy*
  • Humans
  • Injections, Jet
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Patient Satisfaction
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacokinetics*
  • Peptide Fragments / therapeutic use*
  • Therapeutic Equivalency

Substances

  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Peptide Fragments
  • Enfuvirtide