Albuterol pharmacokinetics

SABAs, such as albuterol, are hydrophilic and have onset of action within 5 to 15 minutes after aerosol inhalation, reach peak response within 0.5 to 2 hours, and have a response that is sustained for 4 to 6 hours. Men have a greater volume of distribution for albuterol than women, but African Americans and European Americans have no difference in albuterol pharmacokinetics [9]. In comparison, the onset of bronchodilation is 30 to 50 minutes for LABAs such as salmeterol because of their lipophilicity, a property resulting from the addition of a long side chain. Peak response... 

Mohamed MH, Lima JJ, Eberle LV, et al. Effects of gender and race on albuterol pharmacokinetics. Pharmacotherapy 1999 19 157 61. 

G. Hochhaus, and H. Moellmann, Beta-agonists terbutaline, albuterol, and feno-terol. Handbook of Pharmacokinetic/Pharmacodynamic Correlations (H. Derendorf and G. Hochhaus). CRC, New York, 1995, p. 299. 

Boulton DW, Fawcett JP. Pharmacokinetics and pharmacodynamics of single oral doses of albuterol and its enantiomers in humans. Clin Pharmacol Ther 1997 62(2) 138 I4. 

In humans, the half-life of aerosolized albuterol sulfate is approximately 4 h. The kidney is the primary site of elimination with the majority of the drug excreted as sulfide and glucuronide metabolites (61%) and the remainder (39%) excreted unchanged. The absorption of albuterol from the gastrointestinal tract is poor (20% bioavailability) the primary site of absorption into the systemic circulation is the pulmonary system. There are currently no data available on the pharmacokinetics of albuterol in horses. 

Example Albuterol (Proventil, Ventolin) Route PO, Aerosol Pregnancy category C Pharmacokinetic Absorbed in GI tract, gradual absorption... 

Pirbuterol is the pyridine isostere of albuterol. It has pharmacokinetics similar to albuterol but is half as potent at the p2-receptor. Pirbuterol is only available as an inhaler, whereas albuterol comes in tablet, syrup, solution, and aerosol formulations. Adverse effects of pirbuterol are nervousness, tremor, and headache, which is less than the profile for albuterol, which adds nausea, vomiting, dizziness, hypertension, insomnia, tachycardia, and palpitations. 

The major pharmacokinetic parameters of albuterol and terbutaline are listed in Tables 1 and 2. Irrespective of the route of administration, the pharmacokinetics of racemic albuterol are stereoselective with a faster disappearance of the active R enantiomer from plasma (Tables 1 and 2). This is due to stereoselective metabolism and renal clearance of albuterol in favor of the R enantiomer. Both the total body and renal clearances of R-albuterol are approximately 2 to 3 times higher than those of the distomer, resulting in a >3-fold higher maximum plasma concentrations of... 

In contrast to albuterol, plasma concentrations of R-terbutaline are significantly higher than those of its inactive S enantiomer (Table 1). Borgstrom et al. [117] investigated the plasma pharmacokinetics of terbutaline enantiomers after single IV and oral doses of single enantiomers or the racemate. The IV doses were 0.125 mg of S or R enantiomer or 0.5 mg of the racemate, and oral doses were 5 mg of R- or S-terbutaline or the racemate. Mean steady-state volumes of distribution of enantiomers were similar (1.9L/kg), although mean clearance was 0.19 and 0.13L/h/kg for... 

For some dmgs, we can link the parameters and equations of pharmacokinetics to those of pharmacodynamics, resulting in a PKPD model which can predict pharmacological effect over time. This concept is discussed in more detail later in this chapter. (Equation 17.7 is a typical PKPD equation.) Figure 17.3 depicts the relationship of effect versus time for the dmg albuterol (salbuta-mol) and contrasts this with a superimposed plot of plasma dmg concentration versus time. 

Vaughan, D.E., Pharmacokinetics of Albuterol and Butorphanol Administered Intravenously and via a Buccal Patch. 2003, Texas A M University, College Station, TX. 

It is also true that enantiomers can have different bioactivity, bioavailability, and pharmacokinetics. There are many examples. One is albuterol, used for over 40 years as a racemic mixture to treat asthma. It is the R(-) enantiomer which is the effective bronchodilator. There are some side effects with the use of racemic albuterol. The S(+) enantiomer does not exhibit the beneficial selective binding. At best, it can be considered inert and there is even some indication that it can act as an agonist with effects contrary to the R(-) enantiomer. The S(-l-) enantiomer is metabolized up to 10 times more slowly and therefore persists in the circulation up to 12 hours [31]. Even if the S(+) enantiomer were inert, a patient taking the racemic mixture needs twice the amount versus taking the effective R(-) enantiomer. 

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