Enhancement of oral bioavailability of insulin in humans.
OBJECTIVE
The purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg subcutaneous reference formulation.


METHODS
Twenty five healthy volunteers participated in five studies using a two-phase, two-sequence crossover design with washout period of one day. Mean disposition kinetics was determined by non-compartmental analysis using Kinetica program. Absorption kinetics of insulin products were then determined using SIMCYP simulator utilizing ADAM model.


CONCLUSIONS
Dimensional analysis results showed the superiority of formula 4:2 U/kg oral dose with 57 nm particle size over other oral formulations when compared with subcutaneous route. Optimized intestinal permeability coefficients (x10(-4)) of insulin best test and reference formulations were 0.084 and 0.179 cm/sec respectively. Total fraction of insulin dose absorbed (Fa) for the test and reference products were 3.0% and 19% respectively. Subcutaneous product exhibited higher absorption rate and extent than oral insulin. Yet that was compensated by the increase in other factors such as Fa*, Peff* and oral dose, leading to similar insulin plasma levels and similar effect on glucose infusion rates. Oral insulin bioavailability was shown promising for the development of oral insulin product.
Badwan
Adnan
A
Jordan Pharmaceutical Manufacturing Co., PO Box 94, Naor, Jordan.
Remawi
Mayas
M
Qinna
Nidal
N
Elsayed
Amani
A
Arafat
Tawfiq
T
Melhim
Munther
M
Hijleh
Omar Abu
OA
Idkaidek
Nasir M
NM
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000592:standards; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D012015:Reference Standards; D055815:Young Adult
D007004:Hypoglycemic Agents; D007328:Insulin