Effect of injection site on relative bioavailability of exenatide (synthetic exendin‐4)

Exenatide is an incretin mimetic with glucoregulatory activity in patients with type 2 diabetes. Here we report the results of a randomized, open-label, crossover study to assess the relative bioavailability of subcutaneous exenatide injected into arm or thigh vs abdomen. The study enrolled 28 subjects with type 2 diabetes: age 56.2±8.ly; BMI 33.0±5.1 kg/m2; HbA1c, 8.0±1.7% (±SD). Subjects had a single 10 μg injection of exenatide followed by 10 h of plasma sampling. Geometric LS mean exenatide AUC0-infin values were 63935±6608 pg*min/mL (abdomen; ±SEM), 59573±6157 pg*min/mL (arm), 62148±6424 pg*min/mL (thigh). The AUC geometric LS mean ratio for arm vs abdomen was 0.93 with geometric 90% CI ratios of 0.82 to 1.05; and for thigh vs abdomen was 0.97, geometric 90% CI ratios 0.86 to 1.1. Geometric LS mean exenatide Cmax values were 220±24 pg/mL (abdomen), 218±23 pg/mL (arm), and 193±21 pg/mL (thigh). The Cmax geometric LS mean ratio for arm vs abdomen was 0.99 with geometric 90% CI ratios of 0.85 to 1.15, and for thigh vs abdomen was 0.88, geometric 90% CI ratios 0.75 to 1.02. The most common treatment-emergent adverse events were mild-to-moderate nausea, vomiting, and headache. In summary, all injection sites yielded equivalent pharmacokinetic profiles. Clinical Pharmacology & Therapeutics (2004) 75, P58–P58; doi: 10.1016/j.clpt.2003.11.221