Context. Recombinant human leptin (r-metHuLeptin) has demonstrated efficacy in improving hormonal and metabolic parameters in leptin-deficient states, but pharmacokinetic parameters following subcutaneous administration have not yet been published. In addition, the effect of potential variability across different leptin assays on concentration-dependent pharmacokinetic parameters remains unknown.

Objective. To characterize pharmacokinetic parameters following subcutaneous r-metHuLeptin administration using three commercially available (Linco, DSL and Alpco) leptin assays.

Design, Setting, Patients, and Intervention. We analyzed pharmacokinetic profiles in 5 lean and 5 obese men following subcutaneous administration of physiologic (0.01 mg/kg) and pharmacologic (0.3 mg/kg) doses of r-metHuLeptin.

Main Outcome Measures. Leptin pharmacokinetic parameters.

Results. Measurement of leptin produced typical pharmacokinetic profiles in all assays with time to maximal concentration and half-life of approximately 3 hours. DSL consistently measured leptin higher than Linco, with Alpco measuring intermediate between or similar to Linco. There was high correlation between assays (R² ranging from 0.89 to 0.98, all P<0.01). Concentration-dependent parameters such as maximal concentration, area under the curve, and clearance were significantly different between assays, whereas concentration-independent parameters such as time to maximal concentration and half-life were generally not different.

Conclusions. We report novel data on leptin pharmacokinetic parameters following subcutaneous administration, which will be relevant for the future therapeutic use of r-metHuLeptin. Although commercially available assays demonstrated high correlation, they can provide substantially different measures of leptin levels. This demonstrates the importance of standardizing leptin assays for diagnosing patients with relative leptin deficiency, determining appropriate doses of r-metHuLeptin for administration, and monitoring response to therapy.