Influence of subcutaneous injection site on the steady-state pharmacokinetics of enfuvirtide (T-20) in HIV-1-infected patients.

BACKGROUND

Enfuvirtide is the first in a new class of antiretrovirals (ARVs), the fusion inhibitors, and the first ARV to be administered by subcutaneous (s.c.) injection.

OBJECTIVES

The primary objective of this study was to determine the steady-state pharmacokinetics and relative bioavailability of enfuvirtide following sc injection at three separate anatomical sites: abdomen (A), thigh (B) and arm (C).

STUDY DESIGN

A single-center, open-label, multiple-dose, three-way randomized, crossover study. Twelve HIV-1-infected adults were recruited from three ongoing Phase II enfuvirtide clinical trials and randomized into three groups. Each group continued to receive s.c. injection of enfuvirtide, at a dose of 90 mg twice daily (bid), according to one of three treatment sequences: ABC, BCA or CAB; over three consecutive periods of approximately 7 days each. Plasma concentrations of enfuvirtide and its metabolite (Ro 50-6343) were measured using a validated liquid chromatography-tandem mass spectrometry method.

RESULTS

The relative bioavailability of enfuvirtide, based on AUC12h and abdomen as a reference site, was 101% for thigh and 117% for arm. The AUC12h of Ro 50-6343 ranged from 14 to 16% of that for enfuvirtide. Although injection site reactions (ISRs) were common, the overall grading (based on pain or discomfort) of all reported ISRs was Grade 1 (mild). The incidence of ISRs varied according to the site of injection, as did the signs and symptoms associated with them. No patient required treatment for an ISR.

CONCLUSIONS

Comparability among the three injection sites, in terms of both absorption and the ISR profile, allows HIV-1-infected patients the freedom to choose and to rotate, if necessary, the site of enfuvirtide injection among the three anatomical sites.