Intranasal administration of insulin with phospholipid as absorption enhancer: pharmacokinetics in normal subjects.
The pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C-peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg-1, 0.6 U kg-1, 0.8 U kg-1) in random order on five separate days. Intranasal insulin was absorbed in a dose-dependent manner with a mean plasma insulin peak 23 +/- 7 (+/- SE) min after administration. Mean plasma glucose nadir was seen after 44 +/- 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p less than 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. A dose-dependent suppression of C-peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight.
Drejer
K
K
Novo Research Institute, Novo Nordisk A/S, Bagsvaerd, Denmark.
Vaag
A
A
Bech
K
K
Hansen
P
P
Sørensen
A R
AR
Mygind
N
N
D000042:Absorption; D000281:Administration, Intranasal; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004337:Drug Carriers; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010743:Phospholipids; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D004337:Drug Carriers; D007328:Insulin; D010743:Phospholipids; D005934:Glucagon