Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment

  • Holmes, Gregory
  • Galitz, Lawrence
  • Hu, Peter
  • Lyness, William

  • 1SFBC International, Miami FL, USA.

    2Novo Nordisk Pharmaceuticals Inc., Princeton NJ, USA.

Correspondence Dr Gregory Holmes, SFBC International, 11190 Biscayne Boulevard, Miami, FL 33181–3405, USA.

Abbreviations AUC0–1440, area under the plasma concentration curve; BMI, body-mass index; CLcr, renal clearance of creatinine; CL/F, apparent clearance; CL/F/kg, body weight-adjusted apparent clearance; Cmax, maximal plasma concentration; FBG, fasting blood glucose; GFR, glomerular filtration rate; HI, human insulin; MRT, mean residence time; PK, pharmacokinetics; t½, half life; tmax, time to maximum concentration; Vz/F, apparent volume of distribution.

These pharmacokinetic studies received financial support of Novo Nordisk Inc.

Received 27 May 2004 Accepted 22 February 2005

British Journal of Clinical Pharmacology 60(5):p 469-476, November 2005.

Aims

To assess the effects of body mass index, renal impairment (creatinine clearance), and hepatic impairment (Child-Pugh Score) on the pharmacokinetics of insulin aspart.

Methods

Pharmacokinetics of insulin aspart (injected subcutaneously in the abdomen immediately before a Boost® standardized meal) were characterized in: (1) diabetic subjects with four ranges of BMI values (n = 23); (2) diabetic subjects with varying degrees of renal impairment (normal, n = 6 vs. two ranges of impairment, n = 12); and (3) nondiabetic patients with varying degrees of hepatic impairment (normal, n = 6 vs. three ranges of impairment, n = 18).

Results

There was no correlation between any pharmacokinetic variable and the degree of renal or hepatic impairment. Increasing obesity was associated with a decreased apparent clearance per kg body weight (β = −0.0005, SE = 0.0001; P = 0.002), an increased t½ (β = 3.513, SE = 1.636; P = 0.044), and an increased ln(AUC0−360) and ln(AUC0−1440) (β = 0.030, SE = 0.013; P = 0.032 and β = 0.039, SE = 0.0132; P = 0.006, respectively). However, obesity-related changes were smaller than individual variations in parameters.

Conclusions

Renal impairment, hepatic impairment, or BMI do not affect the pharmacokinetics of insulin aspart in a clinically significant manner.

Copyright © 2005 Blackwell Publishing Ltd.