title: Saliva versus plasma bioequivalence of rusovastatin in humans: validation of class III drugs of the salivary excretion classification system.
abstract: Bioequivalence of rusovastatin in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioequivalence of class III drugs according to the salivary excretion classification system (SECS). Saliva and plasma samples were collected for 72 h after oral administration of rusovastatin 40 mg to 12 healthy humans. Saliva and plasma pharmacokinetic parameters were calculated by non-compartmental analysis. Analysis of variance, 90 % confidence intervals, and intra-subject and inter-subject variability values of pharmacokinetic parameters were calculated using Kinetica program V5. Human effective intestinal permeability was also calculated by SimCYP program V13. Rusovastatin falls into class III (high permeability/low fraction unbound to plasma proteins) and hence was subjected to salivary excretion. A correlation coefficient of 0.99 between saliva and plasma concentrations, and a saliva/plasma concentration ratio of 0.175 were observed. The 90 % confidence limits of area under the curve (AUClast) and maximum concentration (C max) showed similar trends in both saliva and plasma. On the other hand, inter- and intra-subject variability values in saliva were higher than in plasma, leading to the need for a slightly higher number of subjects to be used in saliva studies. Non-invasive saliva sampling instead of the invasive plasma sampling method can be used as a surrogate for bioequivalence of SECS class III drugs when an adequate sample size is used.
authors: College of Pharmacy, University of Petra, PO Box 961343, Amman, Jordan, nidkaidek@uop.edu.jo.
authors: Nasir
authors: N
authors: Idkaidek
authors: Tawfiq
authors: T
authors: Arafat
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D018592:Cross-Over Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D010865:Pilot Projects; D000068718:Rosuvastatin Calcium / Q000493:pharmacokinetics*; D012463:Saliva / Q000378:metabolism*; D065787:Salivary Elimination; D013810:Therapeutic Equivalency
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium