Modulite technology: pharmacodynamic and pharmacokinetic implications.
In the drive to replace chlorofluorinated hydrocarbons (CFCs) by alternative more environmentally friendly propellants in pressurized metered dose inhalers (pMDIs), Chiesi has developed new inhalers using Modulite technology. The aim was to obtain CFC-free pMDIs which are equivalent, in terms of safety and efficacy, to the previous CFC devices at the same dose. When beclometasone dipropionate (BDP) and budesonide Modulite formulations were compared to the equivalent CFC products there was no significant difference in morning serum cortisol or urinary cortisol excretion, at the maximum recommended daily dose (2000 micrograms or 1600 micrograms respectively). Single dose pharmacokinetic studies in both healthy volunteers and asthmatic patients compared systemic exposure (B17MP levels) for BDP-CFC with BDP Modulite and extrafine BDP-HFA (QVAR). B17MP levels for BDP-CFC and BDP Modulite were comparable, but substantially less than that seen with extrafine BDP-HFA. After 6 weeks of treatment in asthmatic patients, B17MP AUC after inhalation of BDP (1000 micrograms twice-daily) from BDP Modulite was comparable with that obtained after BDP-CFC (Becloforte). Plasma profile of BDP and B17MP were similar after inhalation from BDP Modulite with standard actuator or delivered via a spacer, suggesting that pulmonary delivery of BDP to the lung is similar with both actuators.
North West Lung Research Centre, Manchester, U.K.
A
A
Woodcock
D
D
Acerbi
G
G
Poli
D000280:Administration, Inhalation; D000328:Adult; D000335:Aerosol Propellants / Q000493:pharmacokinetics* / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001507:Beclomethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics* / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D009330:Nebulizers and Vaporizers; D013810:Therapeutic Equivalency; D005466:Fluorocarbons
D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone; D019819:Budesonide; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; C094049:apaflurane; D005466:Fluorocarbons