[Studies on the pharmacokinetics and relative bioavailability of salbutamol aerosol in healthy volunteers].
OBJECTIVE
To study the pharmacokinetics and relative bioavailability of salbutamol aerosol in healthy volunteers.


METHODS
An HPLC method for the determination of salbutamol in human plasma was improved. Ten healthy male subjects were enrolled. A randomized, two-way crossover, open design was adopted. After the subjects inhaled or orally administered salbutamol, fourteen blood samples were taken at predetermined time. The concentrations of salbutamol in plasma were determined by HPLC, and then assessed with PCNONLIN software to obtain the pharmacokinetic parameters and relative bioavailability of aerosol versus water solution.


RESULTS
The standard curve was linear over the range 0.2-20 ng.mL-1. The intra- and interassay RSDs were 7.01% and 2.10% at 0.4 ng.mL-1, 2.18% and 5.25% at 4.0 ng.mL-1 and 4.61% and 4.85% at 15.0 ng.mL-1. The recoveries were between 90% and 110%. The pharmacokinetics of salbutamol aersol was described well with a two-compartment model, and the parameters for salbutamol inhaled and orally administered were assessed as follows: Tmax were (0.22 +/- 0.07) h and (1.8 +/- 0.6) h, Cmax were (3.4 +/- 1.1) ng.mL-1 and (3.9 +/- 1.4) ng.mL-1, T1/2 beta were (4.5 +/- 1.5) h and (4.6 +/- 1.1) h, respectively. The AUC0-20 min (inhal) was 7.94 times as high as the AUC0-20 min (p.o.). There were significant differences between Tmax, AUC, K12, K21, alpha and T1/2 alpha (P < 0.05). The relative bioavailability of salbutamol aerosol was 57.23% compared with its oral solution.


CONCLUSIONS
The assay was sensitive, specific, accurate and precise. The absorption process of salbutamol aerosol in human was significantly different from that of the oral solution. It was demonstrated that AUC0-20 min reflected the lung availability of salbutamol inhaler.
Du
X L
XL
Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. xiaoli22@hotmail.com
Zhu
Z
Z
Fu
Q
Q
Li
D K
DK
Xu
W B
WB
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male
D000336:Aerosols; D001993:Bronchodilator Agents; D000420:Albuterol