Objective: To evaluate the effect of peripheral hyperinsulinemia on assessment of pharmacokinetics (PK) and pharmacodynamics (PD) of insulin preparations in euglycemic clamp. Method: A total of 40 healthy male volunteers aged 18-45 years old in West China Hospital between 2015 and 2017 were divided into euglycemic-hyperinsulinaemic clamp (A) group and euglycemic clamp (B) group. Humulin R (0.2 U/kg) was given subcutaneously at steady state of clamp after infusion of short-acting insulin in A group while in B group Humulin R was given subcutaneously without establishment of artificial hyperinsulinemia. The blood glucose was maintained within target range during the whole clamp. Result: Maximum insulin concentration [(667±141) pmol/L vs (267±68) pmol/L, P<0.01] and area under curve (AUC) of insulin concentration [(152±32) nmol·L(-1)·min vs (57±7) nmol·L(-1)·min, P<0.01] in A group were higher while maximum glucose infusion rate (GIR) [(3.70±0.70) mg·kg(-1)·min(-1) vs (7.66±2.11) mg·kg(-1)·min(-1), P<0.01] and AUC of GIR [(931±272) mg/kg vs (1 920±452) mg/kg, P<0.01] were lower compared to B group. The serum C-peptide levels were lower in both groups after administration of insulin compared with baseline. Conclusion: It is not necessary applying euglycemic-hyperinsulinaemic clamp to evaluate the PK/PD of insulin preparations, which may overestimate the PKparameters and underestimate the PD parameters of insulin preparations.
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