Pharmacokinetic profiles of biphasic insulin aspart 30/70 and 70/30 in patients with Type 1 diabetes: a randomized double-blinded crossover study.

AIMS: To compare pharmacokinetic characteristics of two biphasic insulin aspart (BIAsp) formulations: BIAsp30 and BIAsp70 (30% and 70%, respectively, of fast-acting insulin aspart) during 15 days of multiple dosing (thrice daily). METHODS: A total of 22 patients with Type 1 diabetes (nine women, 13 men) aged 41.4 +/- 9.9 years (mean +/- sd) with a diabetes duration of 18.9 (2.3-40.3) years (median and range) completed the randomized, double-blinded, two-period crossover study. On day 1 and day 15 of each treatment period, 24-h serum insulin and glucose profiles were evaluated. Total area under the insulin aspart concentration-time curve (AUC(0-24 h)), AUC after dinner administration stratified into early (AUCdinner(0-6 h)) and intermediate-phase (AUCdinner(6-14 h)), maximum insulin concentration (Cmax), time to maximum insulin concentration (Tmax) after each meal were recorded. RESULTS: On day 15 BIAsp70 was associated with a shorter Tmax, and more than 40% elevated Cmax. Comparing with BIAsp30, AUC(0-24 h) and AUCdinner(0-6 h) were increased by 25% and 28%, respectively, but AUCdinner (6-14 h) was markedly lower for BIAsp70 [BIAsp30/BIAsp70: 1.9; 95% CI (1.42, 2.55)]. Similar findings were also observed on day 1. The fasting or pre-meal serum insulin levels on day 15 tended to be higher with BIAsp30, but the differences were not statistically significant. CONCLUSIONS The pharmacokinetic properties of BIAsp30 and 70 remain constant during 2 weeks of daily administration in patients with Type 1 diabetes. In comparison with BIAsp30, the administration of BIAsp70 results in a shorter time to and larger maximum insulin aspart concentration. Furthermore, total and early post-dinner insulin AUC were greater, whereas late-phase insulin exposure was lower with BIAsp70.