title: Pharmacokinetic bioequivalence of enfuvirtide using a needle-free device versus standard needle administration.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Open-label, randomized, two-period crossover bioequivalence evaluation.
  
  
  METHODS
  Clinical research center.
  
  
  METHODS
  Twenty-seven adults with HIV-1 viral loads below 1000 copies/ml.
  
  
  METHODS
  Each patient received enfuvirtide 90 mg subcutaneously with the B2000 and with the needle-syringe, with a 1-week washout between treatments.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Trimeris, Inc., Morrisville, North Carolina, USA. atrue@trimeris.com
authors.forename: Andrea L
authors.initials: AL
authors.lastname: True
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Chiu
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Demasi
authors.forename: Richard
authors.initials: R
authors.lastname: Stout
authors.forename: Indra
authors.initials: I
authors.lastname: Patel
mesh_terms: D019540:Area Under Curve; D018592:Cross-Over Studies; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007277:Injections, Jet; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013810:Therapeutic Equivalency
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide