Pharmacokinetics of Anakinra in Subjects of Heavier vs. Lighter Body Weights

This trial (20010168) studied how body weight (BW) and body mass index (BMI) influenced the pharmacokinetics (PK) of anakinra. Subjects ( n  = 32) were assigned to four groups ( n  =   8) according to BW and BMI. Randomization was according to a four‐treatment, four‐period, four‐sequence crossover design. The four anakinra injections were 100, 150, and 300 mg s.c. and 100 mg i.v. Plasma samples were measured by enzyme‐linked immunosorbent assay and noncompartmental PK parameters estimated. BW demonstrated the following effects: after i.v. administration, significant effects ( P  < 0.05) were observed for exposure (area under the concentration–time curve from zero to infinity (AUC 0–∞ )), peak plasma concentration (C max ), volume of distribution at steady state, and clearance; whereas after s.c. administration, significant effects ( P  < 0.05) were observed for C max , AUC 0–∞ , terminal half‐life, and estimated apparent clearance. Mean AUC was reduced 24% and 33% for heavier (BW ≥ 100 kg) vs. lighter subjects (BW ≤ 90 kg) after i.v. and s.c. administration, respectively. BMI increased clearance for heavier subjects. For example, mean (SD) plasma clearance of i.v. anakinra increased from 1.17 ± 0.29 to 1.62 ± 0.24 mL/minute/kg ( P  < 0.05) for larger (> 100 kg) obese (BMI > 36) vs. larger (> 100 kg) less obese (BMI < 35) subjects, respectively. Similarly, results following s.c. supported those after i.v. administration. Derived half‐lives increased with higher BW and higher BMI ranging from 3.63 hour for less obese, lighter‐weight subjects to 7.62 hour for obese, heavier‐weight subjects. Absolute bioavailability ranged from 80–92% and was unrelated to BW or BMI. Anakinra exposure is statistically significantly related to BW and to a lesser extent BMI.