Authors: Holmes, Gregory; Galitz, Lawrence¹; Hu, Peter²; Lyness, William²

Source: British Journal of Clinical Pharmacology, Volume 60, Number 5, November 2005 , pp. 469-476(8)

Publisher: Wiley-Blackwell

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 ( = -0.0005, SE = 0.0001; P = 0.002), an increased t_½ ( = 3.513, SE = 1.636; P = 0.044), and an increased ln(AUC_0-360) and ln(AUC_0-1440) ( = 0.030, SE = 0.013; P = 0.032 and  = 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: http://dx.doi.org/10.1111/j.1365-2125.2005.02476.x

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

Publication date: 2005-11-01

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