Pharmacokinetics of recombinant methionyl human leptin after subcutaneous administration: Variation of concentration-dependent parameters according to assay

Context: Recombinant human leptin (r-metHuLeptin) has demonstrated efficacy in improving hormonal and metabolic parameters in leptin-deficient states, but pharmacokinetic parameters after sc 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: The objective of the study was to characterize pharmacokinetic parameters after scr-metHuLeptin administration using three commercially available leptin assays (Linco, Diagnostic Systems Laboratories, and Alpco). Design, Setting, Patients, and Intervention: We analyzed pharmacokinetic profiles in five lean and five obese men after sc administration of physiological (0.01 mg/kg) and pharmacological (0.3 mg/kg) doses of r-metHuLeptin. Results: Measurement of leptin produced typical pharmacokinetic profiles in all assays with time to maximal concentration and half-life of approximately 3 h. Diagnostic Systems Laboratories consistently measured leptin higher than Linco, with Alpco measuring intermediate between or similar to Linco. There was high correlation among assays (R-2 ranging from 0.89 to 0.98, all P < 0.01). Concentrationdependent parameters such as maximal concentration, area under the curve, and clearance were significantly different among 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 after sc 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.