Int J Clin Pharm Th
-
Int J Clin Pharm Th · Feb 2014
Randomized Controlled TrialBioequivalence assessment of two transdermal delivery systems of fentanyl in healthy Chinese volunteers.
The objective of this study was to investigate the bioequivalence of two formulations (generic preparation and Durogesic patch) of 4.2 mg fentanyl. They were assessed in relative bioavailability in 20 healthy Chinese male volunteers according to a single dose, 2-sequence, crossover randomized design. The two formulations were administered at two treatment days, separated by a washout period of 14 days. ⋯ ANOVA and two one-sided t-test procedures showed no significant difference in log-transformed Cmax, AUC0-T and AUC0-∞ while the 90% confidence interval (CI) of the ratio of the geometric means of their values were also used to assess bioequivalence between the two formulations. Based on these statistical inferences it was concluded that the two formulations exhibited comparable pharmacokinetic profiles and that test formulation is bioequivalent to reference formulation. The point estimate (90% CI) of two formulations was: AUC0-T, 96.7% (85 - 105%); AUC0-∞, 97.5% (89 - 110%); Cmax, 96.2% (91 - 104%); tmax, 97.1% (93 - 101%), respectively.
-
Int J Clin Pharm Th · Feb 2014
Randomized Controlled TrialCorrelation of genotype, phenotype, and mRNA expression of CYP2D6 and CYP2C19 in peripheral blood leukocytes (PBLs).
The genetic polymorphism of drug metabolizing enzymes of the cytochrome P450 (CYP) families, especially CYP2D6 and CYP2C19, is the most important cause of variable responses of many drugs. Enzyme activity ranges from complete deficiency, so called poor metabolizers (PMs), to an ultrafast metabolism. While PMs and extensive metabolizers (EMs) can be well distinguished by genotyping, phenotyping is necessary to subdivide EMs from intermediate metabolizers (IMs). The aim of the study was to evaluate if messenger RNA (mRNA) concentration for CYP-enzymes in peripheral blood leukocytes (PBLs) will be predictive of systemic enzyme activity, allowing an easy and safe determination of metabolic activity. ⋯ The results do not support the concept of using mRNA expression profiles for CYP2D6 and CYP2C19 enzymes in PBLs for prediction of systemic enzyme activity.