Influence of purple grape juice in cyclosporine bioavailability.

OBJECTIVE: The present study was designed to investigate the effect of a single purple grape juice administration on cyclosporin A (CyA) oral bioavailability in healthy volunteers. DESIGN: The study followed a two-period crossover design, where the volunteers were randomly assigned to receive 200-mg CyA soft-gelatin capsules with 200 mL of either purple grape juice or water in the first day of the experiment. SETTING AND PATIENTS: Volunteers were kept at the clinical research unit during the blood sampling period and fasted from 10 p.m. until 4 hours after dosing. A washout period of 1 week was observed before the second treatment was administered. MAIN OUTCOME MEASURE: Blood samples were taken before and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 hours after CyA dosing. All meals received during the study day were standardized. Whole blood was assayed to determined CyA concentration using the Emit 2000 Cyclosporine specific immunoassay (Dade Behring Limited, Syva Company, Dade Behring Inc. Cupertino, CA). Pharmacokinetic parameters were determined by noncompartmental analysis from the individual whole blood concentration-time curves after each treatment using Excel 2003 software. Statistical analysis was performed using paired Student t-test (a 5 .05) with the aid of SAS software. RESULTS: Twelve healthy male volunteers were enrolled in the study, with a mean age of 20.6 years (range 19 -23 years). Purple grape juice significantly decreased cyclosporine AUC by 30% and Cmax by 28%. The time to peak blood level and elimination half-life of the drug, however, were not affected. The clearance determined increased around 50%, with purple grape juice. CyA half-life was not affected, indicating that the change observed in clearance (CL/F) was probably due to a change in the absorption (bioavailability) rather than in the elimination process after administration with purple grape juice. CONCLUSION: Purple grape juice decreased AUC and Cmax, whereas half-life was not changed, suggesting that juice affects the absorption and not drug elimination. The above findings are similar to previous data on the effects on CyA pharmacokinetics caused by the ingestion of red wine. Our findings are potentially relevant in the clinic. The intake of CyA with purple grape juice should be discouraged, as drug bioavailability can be decrease by 30%, leading to blood levels below the drug therapeutic window. A free interval of at least 2 hours between CyA intake and purple juice drinking is recommended.

RC-3095, a selective gastrin-releasing peptide receptor antagonist, does not protect the lungs in an experimental model of lung ischemia-reperfusion injury.

RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI) by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR), RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P < 0.001). The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P = 0.005). Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P < 0.013). No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1ß (P = 0.159) and TNF-α (P = 0.260), as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.