IngentaConnect Pharmacokinetics of insulin aspart in obesity, renal impairment, ...

Abstract:

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 ( bgr

= -0.0005, SE = 0.0001; P = 0.002), an increased t_½ ( bgr

= 3.513, SE = 1.636; P = 0.044), and an increased ln(AUC_0-360) and ln(AUC_0-1440) ( bgr

= 0.030, SE = 0.013; P = 0.032 and bgr

= 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. Abbreviations

AUC_0–1440, area under the plasma concentration curve; BMI, body-mass index; CL_cr, renal clearance of creatinine; CL/F, apparent clearance; CL/F/kg, body weight-adjusted apparent clearance; C_max, maximal plasma concentration; FBG, fasting blood glucose; GFR, glomerular filtration rate; HI, human insulin; MRT, mean residence time; PK, pharmacokinetics; t_½, half life; t_max, time to maximum concentration; Vz/F, apparent volume of distribution.

Keywords: dose adjustment; starting dose; insulin analogues; bolus insulin

Document Type: Research article

DOI: 10.1111/j.1365-2125.2005.02476.x

Affiliations: 1: SFBC International, Miami FL 2: Novo Nordisk Pharmaceuticals Inc., Princeton NJ, USA

You have access to the full text article on a website external to Ingentaconnect.

Please click here to view this article on InterScience.

You may be required to register and activate access on InterScience before you can obtain the full text. If you have any queries please contact onlinehelp@oxon.blackwellpublishing.com

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