Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment.
OBJECTIVE
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 (beta = -0.0005, SE = 0.0001; P = 0.002), an increased t((1/2)) (beta = 3.513, SE = 1.636; P = 0.044), and an increased ln(AUC(0-360)) and ln(AUC(0-1440)) (beta = 0.030, SE = 0.013; P = 0.032 and beta = 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.
Holmes
Gregory
G
SFBC International, 11190 Biscayne Boulevard, Miami, FL 33181-3405, USA.
Galitz
Lawrence
L
Hu
Peter
P
Lyness
William
W
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007271:Injections, Intradermal; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D061267:Insulin Aspart; D007674:Kidney Diseases / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart