Clinical effects of locally delivered nicotine in obstructive sleep apnea syndrome.
Obstructive sleep apnea (OSA) is a common disorder characterized by disordered breathing and associated with increased mortality and cardiovascular morbidity. A factor in the pathogenesis of OSA is hypotonia of the upper airway muscles during sleep, resulting in occlusion of the upper airway. Nicotine may be a suitable drug because it is a stimulant of breathing and activity of oropharyngeal muscles. A novel delivery system, a nicotine tooth patch (NTP) that releases nicotine continuously, has been developed by Perio Products (Jerusalem, Israel). A 2-mg NTP achieved low plasma levels of nicotine with high saliva levels (62 microg/mL), presumably resulting in high nicotine levels in the oropharynx. The aim of this study was to evaluate the effect of two doses of NTP, 2 mg and 4 mg, on the clinical features in OSA. Ten subjects with OSA were admitted overnight and monitored by polysomnography at baseline and during two treatments. The treatments were blind and in a randomized order. After a 4.3-mg NTP, T(max) was 40 +/- 16 minutes, C(max) was 123 +/- 43 microg/mL, and terminal T(1/2) was 29 +/- 11 minutes in saliva. Substantial nicotine levels persisted in saliva for approximately 4 hours. There was no effect of nicotine on the apnea-hypopnea index, even during the first 4 hours when there were high levels of nicotine in saliva (26.4 +/- 11.6, 26.8 +/- 19.5, and 26.8 +/- 23), or on sleep stages. Eppworth Sleepiness Scale scores were lower with a 4.3-mg NTP (9.1 +/- 4.5, 9.1 +/- 7.7, and 5.9 +/- 6.5). Locally delivered nicotine at the doses used had no significant effect on OSA.
Zevin
Shoshana
S
Department of Internal Medicine, Shaare Zedec Medical Center, Jerusalem, Israel. szevin@szmc.org.il
Swed
Edwina
E
Cahan
Clement
C
D000279:Administration, Cutaneous; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009123:Muscle Hypotonia / Q000188:drug therapy; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012463:Saliva / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
D018722:Nicotinic Agonists; D009538:Nicotine