Pharmacokinetics and absolute bioavailability of mepolizumab following administration at subcutaneous and intramuscular sites

Abstract This study characterized the pharmacokinetics (PK) of mepolizumab, after a single intravenous (IV), subcutaneous (SC), or intramuscular (IM) dose in healthy adults and determined the absolute bioavailability of SC and IM mepolizumab delivered at different anatomical regions. Sixty healthy subjects were randomly assigned to receive a single dose of either mepolizumab 250 mg by IV, SC injection (upper arm, abdomen, or thigh); or IM injection (thigh). Following IV administration, the mean maximum observed plasma mepolizumab concentration (C max ) and the mean area under the concentration versus time curves from time zero to infinity (AUC (0‐∞) ) were 109 ± 17 µg/mL and 1,557 ± 250 µg d/mL, respectively. After SC administration, the mean (±SD) values of C max and AUC (0‐∞) were 34.1–38.2 ± 7.3–12.1 µg/mL and 1,110–1,238 ± 228–372 µg d/mL, respectively. Following IM administration, the mean values of C max and AUC (0‐∞) were 46.9 ± 10.6 µg/mL and 1,395 ± 348 µg d/mL. The median terminal half‐life was similar for SC, IM and IV administration (17.9–20.4, 19.2, and 18.5 days, respectively). The overall mean bioavailability of SC mepolizumab was 64–75%, and absorption was relatively similar for the three SC injection sites. Mepolizumab 250 mg was generally well tolerated in this study. These results support flexibility in the SC injection site for mepolizumab.