The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.
Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules.
Kraft
Walter K
WK
Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Steiger
Barry
B
Beussink
Don
D
Quiring
John N
JN
Fitzgerald
Nancy
N
Greenberg
Howard E
HE
Waldman
Scott A
SA
D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019819:Budesonide / Q000009:adverse effects / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers
D001993:Bronchodilator Agents; D019819:Budesonide