Comparison of the pharmacokinetic and pharmacodynamic profiles of biphasic insulin aspart 50 and 30 in patients with type 2 diabetes mellitus: A single-center, randomized, double-blind, two-period, crossover trial in Japan

Abstract Background: To overcome the complicated mixing procedures required in the use of insulin formulations, premixed formulations consisting of rapid-acting and intermediate-type insulin in various mixing proportions have been developed. Biphasic insulin aspart 50 (BIAsp50) and 30 (BlAsp30) are...

Full description

Saved in:
Bibliographic Details
Published in:Clinical therapeutics 2007-05, Vol.29 (5), p.927-934
Main Authors: Hirao, Koichi, Maeda, Hajime, Urata, Shinichi, Takisawa, Yukiko, Hirao, Setsuko, Sasako, Tatsuya, Sasaki, Tomio
Format: Article
Language:English
Subjects:
Area Under Curve
Biological and medical sciences
biphasic insulin aspart
Biphasic Insulins
Cross-Over Studies
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - drug therapy
Diabetes. Impaired glucose tolerance
Double-Blind Method
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
euglycemic clamp
Female
Glucose Clamp Technique
glucose infusion rate
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - therapeutic use
Insulin - administration & dosage
Insulin - analogs & derivatives
Insulin - pharmacokinetics
Insulin - therapeutic use
Insulin Aspart
Insulin, Isophane
Internal Medicine
Japan
Male
Medical Education
Medical sciences
Middle Aged
pharmacodynamics
pharmacokinetics
Pharmacology. Drug treatments
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background: To overcome the complicated mixing procedures required in the use of insulin formulations, premixed formulations consisting of rapid-acting and intermediate-type insulin in various mixing proportions have been developed. Biphasic insulin aspart 50 (BIAsp50) and 30 (BlAsp30) are 2 premixed formulations containing the active ingredient insulin aspart (IAsp) and consisting of a rapid-acting component soluble IAsp) and intermediate-acting component (protamine-crystallized protracted IAsp) in ratios of 50/50 and 30/70, respectively. These formulations are provided with the expectation that BIAsp30 and BIAsp50 will be beneficial for patients needing to improve their postprandial blood glucose control without changing their dietary habits and lifestyles. BIAsp30 has been widely used in medical practice, whereas BIAsp50 is being investigated in clinical trials. Objective: The aim of this study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of BIAsp50 (test) and BIAsp30 (reference) after single-dose SC injection in patients with type 2 diabetes mellitus. Methods: This single-center, randomized, doubleblind, 2-period, crossover trial was conducted at the H.E.C. Science Clinic, Yokohama, Japan. Male and female patients aged ⩾20 years with a ⩾ 1-year history of type 2 diabetes were eligible. Patients were randomly assigned to 1 of 2 treatment sequences: group A received BIAsp30 in period 1 and BIAsp50 in period 2; group B received BIAsp50 in period 1 and BIAsp30 in period 2. All treatments were administered as an SC injection of a single dose (0.3 U/kg). The study periods were separated by a washout period of 4 to 21 days. For PK analysis of IAsp (maximum serum IAsp concentration [Cmax,IAsp ; primary end point], AUC of serum IAsp 0 to 120, 240, and 480 minutes after administration [AUC0–120 min,IAspl , AUC0–240 min,IAsp , and AUC0–480 min,IAsp5 respectively], and time toCmax,IAsp [Tmax,IAsp ] ), blood samples were drawn immediately before (baseline) and at prespecified time points over 480 minutes after administration. The PD profiles of BIAsp50 and BIAsp30 were also examined by comparing the time course of the glucose infusion rate (GIR) using the euglycemic clamp technique. The PD end points were AUC of GIR 0 to 120 minutes after administration (AUC0–120 min,GIR ), maximum GIR (GIRmax ), and time to GIRmax (Tmax,GIR ). Tolerability was assessed using physical examination, including vital sign measurement, electrocardio
ISSN:0149-2918
1879-114X
DOI:10.1016/j.clinthera.2007.05.017