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Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment
Author(s) -
Holmes Gregory,
Galitz Lawrence,
Hu Peter,
Lyness William
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02476.x
Subject(s) - medicine , renal function , pharmacokinetics , endocrinology , body mass index , insulin , area under the curve , obesity , creatinine , insulin aspart , postprandial
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 t ½ (β = 3.513, SE = 1.636; P = 0.044), and an increased ln(AUC 0−360 ) and ln(AUC 0−1440 ) (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. 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.