Pharmacokinetics and pharmacodynamics of insulin aspart in patients with type 2 diabetes: assessment using a meal tolerance test under clinical conditions.
1. Few studies have evaluated the pharmacokinetics of rapid-acting insulin analogues in patients with Type 2 diabetes, especially under clinical conditions. The aim of the present study was to assess both the pharmacokinetics and pharmacodynamics of insulin aspart in Type 2 diabetic patients who were being treated with the analogue alone. 2. Meal tolerance tests with and without self-injection of a customary dose of insulin aspart (0.05-0.22 U/kg) were conducted in 20 patients in a randomized cross-over study. 3. The dose of insulin aspart (per bodyweight) was significantly correlated with both the maximum concentration (r(2) = 0.59; P < 0.01) and area under the concentration-time curve for insulin aspart (r(2) = 0.53; P < 0.01). However, the time to maximum concentration (T(max)), which varied widely from < 60 to ≥ 120 min, was not associated with either dosage (r(2) = 0.02; P = 0.51) or body mass index (r(2) = 0.02; P = 0.57). Injection of insulin aspart exacerbated delayed hyperinsulinaemia after meal loading, mainly in patients with T(max) ≥ 120 min. With regard to pharmacodynamics, insulin aspart had favourable effects on postprandial hyperglycaemia, hyperglucagonaemia and hyperlipidaemia. 4. The T(max) for this insulin analogue differed greatly between individuals and delayed hyperinsulinaemia was particularly exacerbated in patients with higher T(max) values. Identification of the factors contributing to interindividual variation in the absorption lag time is essential for improving the efficacy and safety of insulin aspart.
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. h-ando@jichi.ac.jp
Hitoshi
H
Ando
Seiichiro
S
Kurita
Akiko
A
Shimizu
Ken-ichiro
K
Kato
Kazuhide
K
Ishikura
Koumei
K
Taji
Masafumi
M
Uno
Yumie
Y
Takeshita
Hirofumi
H
Misu
Akio
A
Fujimura
Shuichi
S
Kaneko
Toshinari
T
Takamura
D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D061267:Insulin Aspart / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology*
D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart