Absorption of Drugs Given for Local Lung Effect

¡-Adrenergic Agonists. Systemic absorption of inhaled adrenergic agonists is a well-described phenomenon. After inhalation of albuterol, 180 mg, by normal subjects, the mean peak level of 1469 ± 410 pg was attained in an average of 13 minutes [119].

Systemic side effects such as tachycardia with isoproterenol inhalation, mild systolic hypertension and tachycardia with ¡2-specific agonists, and the tremor seen with ¡2-adrenergic receptor agonists all are caused by hematogenous dissemination of inhaled drug. Absorption of drug from its aerosol deposition site followed by hematogenous delivery to obstructed airways might contribute to the action of ¡2-adrenergic agonists [120].

Cromolyn. One would not ordinarily consider cromolyn to have any action other than local, but higher-cromolyn blood correlates with better clinical efficacy [121]. Delivery methods affect cromolyn delivery. Disodium cromoglycate (20 mg) delivered to normal subjects via nebulized aerosol as nebulizer solution only, nebulizer solution with saline, or nebulizer solution plus a beta 2 agonist yielded, respectively, peak levels of 8.8, 17.2, or 24.5ng/mL [122]. The clinical relevance of these data is not clear.

Inhaled Steroids. Inhaled steroids used in asthma can also be absorbed after aerosol dosing. A major disadvantage of inhaled steroids is that when given in relatively high doses, there is sufficient systemic absorption to cause adrenal suppression. Pharmacological modification that reduces systemic absorption without impairing local anti-inflammatory activity could be important. Evidence examining other inhaled substances suggests that absorption is more rapid from more peripheral sites [123,124] but that total absorption may be quantitatively similar from all sites [124].

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