Efficient Evaluation of In Vivo Performance in Human for Generic Formulation by Novel Dissolution-Absorption Prediction (DAP) Workflow.

PURPOSE: The pharmaceutical bioequivalence of generic medicines must be confirmed with corresponding original drugs. Although the in vitro dissolution tests are required, results of the mandatory in vitro study do not necessarily reflect the in vivo performance after oral administration. Then, we have tried to develop the novel "Dissolution-Absorption Prediction (DAP) workflow" to evaluate the in vivo performance of generic medicines. METHODS: The DAP workflow consists of an "In vitro two-cell connected dissolution (TCCD) system" mimicking the changes in the luminal pH associated with gastrointestinal transit of medicines, "Evaluation of pharmacokinetics of active pharmaceutical ingredient (API)" and "Prediction of plasma concentration-time profile". TCCD system-evaluated dissolution kinetics of APIs from generic formulations and pharmacokinetic parameters based on human data regarding the original drugs were used to calculate the plasma concentration-time profiles of APIs after the oral administration of generic medicines. RESULTS: The mandatory in vitro dissolution tests indicated that the dissolution properties of valsartan (BCS class II) and fexofenadine (BCS class III/IV) in generic formulations did not coincide with those in the corresponding original formulations. The TCCD system provided the very similar dissolution kinetics for the generic and original formulations for the two APIs. Plasma concentration-time profiles evaluated utilizing the dissolution profiles obtained by the TCCD system were in good agreement with the observed profiles for both the generic and original formulations for each API. CONCLUSIONS: The DAP workflow would be valuable for estimating the in vivo performance of generic formulation and deducing their bioequivalence with the original formulation.

Families' and physicians' predictions of dialysis patients' preferences regarding life-sustaining treatments in Japan.

BACKGROUND: Substituted judgment traditionally has been used often for patient care in Japan regardless of the patient's competency. It has been believed that patient preferences are understood intuitively by family and caregivers. However, there are no data to support this assumption. METHODS: A questionnaire survey was administered to 450 dialysis patients in 15 hospitals to determine their preferences for cardiopulmonary resuscitation (CPR) and dialysis therapy under various circumstances. Simultaneously, we asked family members and physicians of these patients about patient preferences to evaluate their ability to predict what their patients would want. The accuracy of families' and physicians' judgments was assessed by means of kappa coefficient. RESULTS: Three hundred ninety-eight pairs, consisting of a patient, 1 of his or her family members, and the physician in charge, participated from 15 hospitals in Japan, with a response rate of 88%. Sixty-eight percent of family members correctly predicted patients' current preferences for CPR, 67% predicted patients' preferences for dialysis when they were severely demented, and 69% predicted patients' preferences for dialysis when they had terminal cancer. Corresponding figures for physicians were 60%, 68%, and 66%. When using kappa coefficient analysis, those results indicated that neither family members nor physicians more accurately predicted their patients' wishes about life-sustaining treatments than expected by chance alone. (All kappa coefficients <0.4.) CONCLUSION: Our study suggests that patients who want to spend their end-of-life period as they want should leave better advance directives.

Influence of family on acceptance of influenza vaccination among Japanese patients.

BACKGROUND: Influenza is a major cause of morbidity and mortality in Japan and worldwide, especially for people of >65 years old and those with high-risk medical conditions. Although the influenza vaccine is effective in reducing the morbidity and mortality, the vaccine coverage rate has not increased adequately in Japan, compared with western countries. OBJECTIVE: Our aim was to assess whether medical and personal characteristics are associated with receiving influenza vaccination in Japanese patients. METHODS: Out-patients of a city hospital were recruited for a case-control study between November 1998 and February 1999. Cases were 98 out-patients aged 18 years or older who received influenza vaccination. Controls were 112 non-vaccinated out-patients matched with cases for primary physician and date of clinic visit. The candidates were interviewed by telephone and asked to respond to a 26-item questionnaire. The data were analysed using multiple logistic regression models. RESULTS: The factors associated with the acceptance of influenza vaccination were: (i) recommendation by a family member and/or a close friend [odds ratio (OR) 17.74; 95% confidence interval (CI) 1.95-161.77]; (ii) belief in influenza vaccine efficacy (OR 10.55; 95% CI 3.42-32.49); (iii) having a family member and/or friends who had been vaccinated before (OR 6.44; 95% CI 2.37-17.50); (iv) physician's recommendation (OR 4.03; 95% CI 1.42-11.37); and (v) knowledge about the influenza vaccine (OR 3.06; 95% CI 1.02-9.20). Fear of adverse reactions (OR 0.21; 95% CI 0.07-0.66) was the sole factor associated with non-acceptance of influenza vaccine. CONCLUSION: Patients in Japan are likely to be greatly influenced by their family members or close friends in their decision of whether to accept influenza vaccination, unlike US patients who make health care decisions on their own. When implementing an influenza vaccination programme, this effect of cultural background observed in Japan should be taken into account in other countries.