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.

Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy.

BACKGROUND: This study assessed the use of low-energy laser in the prevention or reduction of the severity of oral mucositis. PROCEDURE: A randomized clinical trial was carried out. Patients from 3 to 18 years of age treated with chemotherapy or hematopoietic stem-cell transplantation between May, 2003 and February, 2005 were eligible. The intervention group received laser application for 5 days following the start of chemotherapy. The grade of oral mucositis was assessed by the WHO per NCI-CTC common toxicity criteria and the assessments were made on days 1, 8 and 15 by a trained examiner blind to the intervention. RESULTS: Sixty patients were evaluable for analysis; thirty-nine (65%) were males, 35 (58%) patients had a diagnosis of leukemia or lymphoma, and 25 (42%) had solid tumors. The mean age was 8.7 +/- 4.3 years. Twenty-nine patients were randomized in the laser group and 31 in the control group. On day 1, no patients presented with mucositis. On day 8, of 20 patients (36%) who developed mucositis, 13 of them were from the laser group and 7 from the control group. On day 15, of 24 patients (41%) who developed mucositis, 13 of them were from the laser group and 11 from the control group. There was no significant difference between groups concerning the grades of mucositis on day 8 (P = 0.234) or on day 15 (P = 0.208). CONCLUSIONS: This study showed no evidence of benefit from the prophylactic use of low-energy laser in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care was provided.