The effect of smoking cessation and subsequent resumption on absorption of inhaled insulin.
OBJECTIVE
To assess the absorption profile of inhaled insulin in healthy, actively smoking subjects at baseline, after smoking cessation, and after smoking resumption and compare it with nonsmoking subjects.


METHODS
Insulin pharmacokinetics and glucodynamics were measured in 20 male smoking subjects (10-20 cigarettes/day) and 10 matched nonsmoking subjects after receiving inhaled insulin (1 mg) or the approximate subcutaneous insulin equivalent (3 units) in a randomized cross-over fashion. All smokers then received inhaled insulin 12 h, 3 days, and 7 days into a smoking cessation period. They then resumed smoking for 2-3 days before again receiving inhaled insulin 1 h after the last cigarette.


RESULTS
Before smoking cessation, maximum insulin concentration (Cmax) and area under the curve (AUC) for insulin concentration time (AUC-Insulin(0-360)) with inhaled insulin were higher, and time to Cmax (t(max)) shorter, in smokers than nonsmokers (Cmax 26.8 vs. 9.7 microU/ml; AUC-Insulin(0-360) 2,583 vs. 1,645 microU x ml(-1) x min(-1); t(max) 20 vs. 53 min, respectively; all P < 0.05), whereas with subcutaneous insulin, systemic exposure was unchanged (AUC-Insulin(0-360) 2,324 vs. 2,269 microU x ml(-1) x min(-1); P = NS). After smoking cessation, AUC-Insulin(0-360) decreased with inhaled insulin by up to 50% within 1 week and approached nonsmoker levels. Cmax decreased and t(max) increased relative to baseline but were still not comparable with nonsmoker values. Smoking resumption completely reversed the effect of smoking cessation. Glucodynamics corroborated the observed findings in insulin pharmacokinetics.


CONCLUSIONS
Cessation and resumption of smoking greatly altered the pharmacokinetics of inhaled insulin. As rapid changes in systemic insulin exposure increase hypoglycemia risk, inhaled insulin should not be used in people with diabetes who choose to continue smoking. This is consistent with recommendations that people with diabetes refrain from smoking altogether.
Becker
Reinhard H A
RH
Clinical Discovery and Human Pharmacology, Aventis Pharma Deutschland, Industriepark Höchst, Building H831, Room C0441, 65926 Frankfurt am Main, Germany. reinhard.becker@sanofi-aventis.com
Sha
Sue
S
Frick
Annke D
AD
Fountaine
Robert J
RJ
D000042:Absorption; D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D012016:Reference Values; D012907:Smoking / Q000097:blood*; D016540:Smoking Cessation
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin