Systemic concentrations of salbutamol and HFA-134a after inhalation of salbutamol sulfate in a chlorofluorocarbon-free system.
The objective of this study was to determine if salbutamol was absorbed from a new salbutamol sulfate chlorofluorocarbon (CFC)-free metered-dose inhaler (MDI). Measurement of HFA-134a, the CFC-free propellant, was included to provide proof of delivery of this MDI. Eight healthy men received two inhalations (90 micrograms salbutamol base equivalents per inhalation ex adapter) from the CFC-free inhaler (MDI A) in period 1 and from a reference CFC inhaler (MDI V) in period 2. Eight postdose samples were collected for the determination of salbutamol serum levels over a 4-h period. Salbutamol levels were not quantifiable in most samples. Four subjects given MDI A and two given MDI V had a few transient salbutamol levels, which occurred in the first hour after dosing, within a narrow range of 1-2 ng/ml and close to the lower limit of detection (1 ng/ml). No pharmacokinetic analyses were possible. Blood samples were also collected after MDI A for propellant quantitation. HFA-134a levels were seen in all subjects, verifying absorption. We conclude that the transient salbutamol serum levels can be attributed to the two-inhalation dose and not to either propellant system.
Harrison
L I
LI
Department of Drug Metabolism, 3M Pharmaceuticals, St. Paul, Minnesota 55144-1000, USA.
Cline
A
A
Wells
T M
TM
Jacobson
J P
JP
Cooper
K M
KM
Chang
S F
SF
Nelson
J R
JR
Ekholm
B P
BP
Morganroth
J
J
D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000335:Aerosol Propellants; D000420:Albuterol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005617:Chlorofluorocarbons, Methane; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D005466:Fluorocarbons
D000318:Adrenergic beta-Agonists; D000335:Aerosol Propellants; D000420:Albuterol; D005617:Chlorofluorocarbons, Methane; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons