caa a22 4500 47581889X CHVBK 20180406123817.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s002280000159 doi (NATIONALLICENCE)springer-10.1007/s002280000159 Pharmacokinetics and pharmacodynamics of a premixed formulation of soluble and protamine-retarded insulin aspart [Elektronische Daten] [L. V. Jacobsen, B. Søgaard, A. Riis] Objective: With the aim to obtain a premixed rapid-acting insulin with a serum insulin profile more closely resembling the endogenous meal-stimulated serum insulin profiles, a 30/70 (rapid/intermediate-acting) premixed suspension of the rapid-acting insulin analogue insulin aspart (BIAsp30) was compared with a similar premixed suspension of biphasic human insulin 30/70 (BHI30) after a single subcutaneous injection. Methods: The study had a randomised, double-blind, two-period crossover design. Twenty-four healthy male subjects received a single subcutaneous dose of either 0.2 U · kg−1 bodyweight of BIAsp30 or BHI30 on two study days. Results: BIAsp30 was absorbed faster than BHI30, as reflected in the area under the insulin concentration-time curve from 0 to 90 min after dosing [AUC(0-90 min)]. This was significantly larger for BIAsp30 than for BHI30 (1403 ± 372 versus 752 ± 191 mU · l−1 · min−1 [mean ± SD]; P < 0.0001). Furthermore, the time to maximum serum insulin concentration (tmax) of BIAsp30 was approximately half the tmax of BHI30 (60 [45-70] versus 110 [90-180] min [median, interquartile range]; P=0.0001) and the maximum insulin concentration (Cmax) was significantly higher for BIAsp30 than for BHI30 (23.4 ± 5.3 versus 15.5 ± 3.7 mU · l−1 [mean ± SD]; P < 0.0001). The serum glucose profiles showed a significantly earlier onset of the glucose-lowering effect following BIAsp30 than following BHI30. Conclusions: The improved absorption properties of soluble insulin aspart in its premixed formulation provide a basis for a more efficient meal-related glucose control and immediate pre-meal delivery when compared with a similar human premixed insulin in the treatment of diabetes mellitus. Springer-Verlag Berlin Heidelberg, 2000 Key words Biphasic insulin aspart 30 nationallicence Premix nationallicence Insulin analogue nationallicence Jacobsen L. V. Clinical Drug Development, Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd, Denmark Tel.: +45-4-4448888; Fax: +45-4-4490555, DK aut Søgaard B. Clinical Drug Development, Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd, Denmark Tel.: +45-4-4448888; Fax: +45-4-4490555, DK aut Riis A. Clinical Drug Development, Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd, Denmark Tel.: +45-4-4448888; Fax: +45-4-4490555, DK aut https://doi.org/10.1007/s002280000159 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000159 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jacobsen L. V. Clinical Drug Development, Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd, Denmark Tel.: +45-4-4448888; Fax: +45-4-4490555, DK aut NATIONALLICENCE 700 1- Søgaard B. Clinical Drug Development, Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd, Denmark Tel.: +45-4-4448888; Fax: +45-4-4490555, DK aut NATIONALLICENCE 700 1- Riis A. Clinical Drug Development, Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd, Denmark Tel.: +45-4-4448888; Fax: +45-4-4490555, DK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer