title: Equivalence of pharmacokinetic characteristics and bronchodilating effect between two combined formulations of nedocromil sodium and salbutamol: MDI and nebulizer solution.
abstract: The aim of this study was to determine the equivalence of single doses of two nedocromil sodium/salbutamol combined formulations, namely (a) metered dose inhaler (MDI) (nedocromil sodium 4 mg + salbutamol 0.2 mg) and (b) nebulizer solution (nedocromil sodium 10 mg + salbutamol 1.5 mg), in a group of healthy volunteers. The plasma pharmacokinetic profiles of nedocromil sodium and the pharmacodynamic effect (bronchodilation) of salbutamol were evaluated. Twelve healthy volunteers entered this randomized, cross-over study. All subjects completed the pharmacokinetic section of the study. Nine of them completed also the pharmacodynamic part of the study. After preliminary controls, treatments were administered on separate days and in random order. Blood samples were collected 5, 10, 20, 30, 45 min, 1, 1.5, 2, 3 and 4h after test medication. Specific airways resistance (sRaw) was measured 5, 10, 20, 30, 40, 50 and 60 min following test treatment administration. The pharmacokinetic profiles of nedocromil sodium were evaluated using the maximum plasma concentration (Cmax), the time to peak plasma concentration (tmax) and the area under the curve from 0 to infinity (AUCzero-->infinity), derived from the plasma concentration/time curves. The bronchodilating effect of the two test treatments were evaluated as sRaw percentage change at each time point, maximum sRaw percentage change (sRawMAX) and area under the curve (AUC) of sRaw percentage change plotted against the time of recording. The mean pharmacokinetic results for MDI and nebulizer solution were, respectively: Cmax = 7.59 ng.ml-1 +/- 4.99 and 9.64 ng.ml-1 +/- 5.22 (p = 0.36), tmax = 0.21 hour +/- 0.08 and 0.28 hour +/- 0.14 (p = 0.19), AUCzero-->infinity = 6.28 ng.ml-1.h +/- 2.91 and 12.91 ng.ml-1.h +/- 4.12 (p = 0.008), while the mean pharmacodynamic results were: sRawMAX = -37.91% +/- 13.77 and -39.69% +/- 9.69 (p = 0.69), AUC = -1465.5 delta %.h +/- 799.3 and -1683.4 delta %.h +/- 496.3 (p = 0.45). No statistically significant differences between treatments were found also for sRaw percentage change at each time point. The absorption of nedocromil sodium was proportional to the two administered nominal doses and similar to values obtained after administration of nedocromil sodium alone. The two combined formulations of nedocromil sodium and salbutamol produce an equivalent bronchodilating effect. These results confirm the pharmacological equivalence of the two products, whichever may be used according to specific therapeutic needs.
authors.affiliation: Medical Department, Fisons Italchimici S.p.A., Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Reggio
authors.forename: S
authors.initials: S
authors.lastname: Bustacchini
authors.forename: R
authors.initials: R
authors.lastname: Pistelli
authors.forename: S
authors.initials: S
authors.lastname: Valente
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D017835:Nedocromil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D017835:Nedocromil; D000420:Albuterol