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- Title
Pharmacokinetics of human leptin in mice and rhesus monkeys.
- Authors
Ahrén, B; Baldwin, R M; Havel, P J
- Abstract
OBJECTIVE: The pharmacokinetic characteristics of human leptin were examined in rhesus monkeys and in C57BL/6J mice fed a normal chow or a high-fat diet. DESIGN: For the monkey study, in nine rhesus monkeys (body weight 12.4±2.4 kg; mean±s.d.), recombinant methuman leptin was injected intravenously or subcutaneously (1 mg/kg). For the mouse study, after 6 months of feeding C57BL/6J mice a high-fat diet (body weight 32.9±3.6 g; n=8) or a control diet (24.5±1.2 g; n=6), recombinant methuman leptin was administered intraperitoneally (10 µg/g). Blood samples were collected for leptin measurement at specific time points after leptin administration. MEASUREMENTS: Plasma leptin concentrations were determined by radioimmunoassay and pharmacokinetic analysis was performed. RESULTS: Disposition of human leptin in rhesus monkeys was biphasic following intravenous administration, with a terminal phase half-life of 96.4±16.5 min and clearance of 1.8±0.2 ml/min/kg. Subcutaneously administered leptin was absorbed slowly, perhaps by a zero-order process as leptin levels appeared to plateau and remained elevated throughout the 8 h sampling period. In C57BL/6J mice, the absorption and elimination of human leptin were both firstorder following intraperitoneal administration. Pharmacokinetic parameters did not differ between normal-weight mice fed a chow diet and obese mice fed a high-fat diet. The elimination half-life was 47.0±26.4 min in mice fed a highfat diet and 49.5±12.0 min in mice fed a control diet. CONCLUSION: The kinetics of leptin in rhesus monkeys were biphasic and clearance was similar to values previously reported in humans. The estimated half-life was 96.4 min in rhesus monkeys and 49.5 min in normal weight mice. The was no difference in leptin kinetics between high-fat fed and control mice, suggesting that the increased baseline leptin levels in the obese mice are due to increased leptin production and...
- Subjects
LEPTIN; PHARMACOKINETICS; RHESUS monkeys
- Publication
International Journal of Obesity & Related Metabolic Disorders, 2000, Vol 24, Issue 12, p1579
- ISSN
0307-0565
- Publication type
Article