Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs.

BACKGROUND: The extents of generic-reference and generic-generic average bioequivalence and intra-subject variation of on-market drug products have not been prospectively studied on a large scale. METHODS: We assessed bioequivalence of 42 generic products of 14 immediate-release oral drugs with the highest number of generic products on the Saudi market. We conducted 14 four-sequence, randomized, crossover studies on the reference and three randomly-selected generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin, clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole, paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum concentration (Cmax) and area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to Cmax time of reference product (AUCReftmax) were calculated using non-compartmental method and their 90% confidence intervals (CI) were compared to the 80.00%-125.00% bioequivalence range. Percentages of individual ratios falling outside the ±25% range were also determined. RESULTS: Mean (SD) age and body-mass-index of 700 healthy volunteers (28-80/study) were 32.2 (6.2) years and 24.4 (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs failed to show bioequivalence. Average geometric mean ratio deviation from 100% was ≤3.2 and ≤5.4 percentage points for AUCI and Cmax, respectively, in both generic-reference and generic-generic comparisons. Individual generic/reference and generic/generic ratios, respectively, were within the ±25% range in >75% of individuals in 79% and 71% of the 14 drugs for AUCT and 36% and 29% for Cmax. CONCLUSIONS: On-market generic drug products continue to be reference-bioequivalent and are bioequivalent to each other based on AUCT, AUCI, and Cmax but not AUCReftmax. Average deviation of geometric mean ratios and intra-subject variations are similar between reference-generic and generic-generic comparisons. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01344070 (registered April 3, 2011).

Typology of end-of-life priorities in Saudi females: averaging analysis and Q-methodology.

BACKGROUND: Understanding culture-and sex-related end-of-life preferences is essential to provide quality end-of-life care. We have previously explored end-of-life choices in Saudi males and found important culture-related differences and that Q-methodology is useful in identifying intraculture, opinion-based groups. Here, we explore Saudi females' end-of-life choices. METHODS: A volunteer sample of 68 females rank-ordered 47 opinion statements on end-of-life issues into a nine-category symmetrical distribution. The ranking scores of the statements were analyzed by averaging analysis and Q-methodology. RESULTS: The mean age of the females in the sample was 30.3 years (range, 19-55 years). Among them, 51% reported average religiosity, 78% reported very good health, 79% reported very good life quality, and 100% reported high-school education or more. The extreme five overall priorities were to be able to say the statement of faith, be at peace with God, die without having the body exposed, maintain dignity, and resolve all conflicts. The extreme five overall dis-priorities were to die in the hospital, die well dressed, be informed about impending death by family/friends rather than doctor, die at peak of life, and not know if one has a fatal illness. Q-methodology identified five opinion-based groups with qualitatively different characteristics: "physical and emotional privacy concerned, family caring" (younger, lower religiosity), "whole person" (higher religiosity), "pain and informational privacy concerned" (lower life quality), "decisional privacy concerned" (older, higher life quality), and "life quantity concerned, family dependent" (high life quality, low life satisfaction). Out of the extreme 14 priorities/dis-priorities for each group, 21%-50% were not represented among the extreme 20 priorities/dis-priorities for the entire sample. CONCLUSION: Consistent with the previously reported findings in Saudi males, transcendence and dying in the hospital were the extreme end-of-life priority and dis-priority, respectively, in Saudi females. Body modesty was a major overall concern; however, concerns about pain, various types of privacy, and life quantity were variably emphasized by the five opinion-based groups but masked by averaging analysis.