Pharmacokinetics of human leptin in mice and rhesus monkeys

B. Ahrén, R. M. Baldwin, Peter J Havel

Research output: Contribution to journalArticle

34 Citations (Scopus)

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±2.4kg, 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±1.2g; 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 first-order 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 high-fat 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 secretion.

Original languageEnglish (US)
Pages (from-to)1579-1585
Number of pages7
JournalInternational Journal of Obesity
Volume24
Issue number12
StatePublished - 2000

Fingerprint

Leptin
Macaca mulatta
leptin
pharmacokinetics
Pharmacokinetics
mice
High Fat Diet
high fat diet
Inbred C57BL Mouse
half life
Half-Life
Obese Mice
Diet
Body Weight
diet
kinetics
Weights and Measures
body weight
intraperitoneal injection
radioimmunoassays

Keywords

  • Leptin
  • Mice
  • Monkeys
  • Pharmacokinetic

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

Cite this

Pharmacokinetics of human leptin in mice and rhesus monkeys. / Ahrén, B.; Baldwin, R. M.; Havel, Peter J.

In: International Journal of Obesity, Vol. 24, No. 12, 2000, p. 1579-1585.

Research output: Contribution to journalArticle

Ahrén, B. ; Baldwin, R. M. ; Havel, Peter J. / Pharmacokinetics of human leptin in mice and rhesus monkeys. In: International Journal of Obesity. 2000 ; Vol. 24, No. 12. pp. 1579-1585.
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N2 - 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±2.4kg, 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±1.2g; 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 first-order 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 high-fat 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 secretion.

AB - 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±2.4kg, 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±1.2g; 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 first-order 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 high-fat 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 secretion.

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