Sanjeev Kaul — Page 2 | Search PubMed

PubMed2002

Effect of food on the oral bioavailability of didanosine from encapsulated enteric-coated beads.

The objective of this study was to assess the effect of food and timing of meals on the bioavailability of didanosine from encapsulated enteric-coated beads. Four different independent, open-label, single-dose, randomized, crossover studies were conducted in healthy subjects (n = 20-30). Didanosine (400 mg) was given concomitantly with a high-fat meal, light meal, yogurt, and applesauce. In addition, didanosine was given 1, 1.5, 2, and 3 hours before and 2 hours after a light meal. Statistical comparison with fasting conditions was made using the equivalence approach for Cmax (70%-143%) and AUC (80%-125%). The high-fat meal, light meal, yogurt, and applesauce decreased the Cmax by 46%, 22%, 30%, and 24%, respectively, and lowered the AUC by 19%, 27%, 20%, and 18%, respectively; statistical analyses indicated an indeterminate food effect, except for the Cmax for the high-fat meal. For 1 hour before meal, Cmax and AUC were lower by 15% and 24% and, for 2 hours after meal, were lower by 15% and 10%, respectively. There was an indeterminate food effect for 1 hour before the meal treatment; in addition, 2 hours after the meal, treatment approached statistical equivalence, missing narrowly on the lower bounds. For 1.5, 2, and 3 hours before meal treatments, Cmax values were unchanged, but AUC was lower by 10%, 4%, and 0%, respectively; lack of food effect was observed for all three treatments. Across studies, median time to Cmix ranged from 1.67 to 2.67 hours but was delayed by 2.5 to 3 hours with high-fat and light meals compared to fasting conditions. The half-life of didanosine was 1.5 to 2 hours. It was concluded that the bioavailability of didanosine from encapsulated enteric-coated beads was reduced by approximately 20% to 25% with food, which can be circumvented by taking didanosine on an empty stomach. The clinical significance of such moderate reductions in didanosine exposure with food, especially as part of a highly active antiretroviral therapy, is not clear.

Administration, Oral↗

PubMedDate not supplied

Angiographic findings and embolotherapy in renal arterial trauma.

PURPOSE: To evaluate the angiographic findings and embolotherapy in the management of traumatic renal arterial injury. METHODS: This is a retrospective review of 22 patients with renal trauma who underwent arteriography and percutaneous embolization from December 1995 to January 2002. Medical records, imaging studies and procedural reports were reviewed to assess the type of injury, arteriographic findings and immediate embolization results. Long-term clinical outcome was obtained by communication with the trauma physicians and by clinical chart review. RESULTS: Arteriography was performed in 125 patients admitted to a State Trauma Center with suspected internal bleeding. Renal arterial injury was documented in 22 and was the result of a motor-vehicle accident (10), auto-pedestrian accident (1), gunshot (4) or stab wounds (6) and a fall (1). Percutaneous renal arterial embolization was undertaken in 22 of 125 (18%) patients to treat extravasation (11), arterial pedicle rupture (5), abnormal arteriovenous (3) or arteriocalyceal (2) communication and pseudoaneurysm (3). One of the pseudoaneurysms and one of the arteriovenous fistulae were found in addition to extravasation. All 22 patients (16 men, 6 women) were hemodynamically stable, or controlled during arteriography and embolotherapy. Selective and/or superselective embolization of the abnormal vessels was performed using coils in 9 patients, microcoils in 9 patients and Gelfoam pledgets in 3 patients. In one patient Gelfoam pledgets mixed with polyvinyl alcohol (PVA) particles were used for embolization. Immediate angiographic evidence of hemostasis was demonstrated in all cases. Two initial technical failures were treated with repeat arteriography and embolization. There was no procedure-related death. There was no non-target embolization. One episode of renal abscess after embolization was treated by nephrectomy and 3 patients underwent elective post-embolization nephrectomy to prevent infection. Follow-up ranged from 1 month to 7 years (mean 31 months). No procedure-related or delayed onset of renal insufficiency occurred. CONCLUSION: In hemodynamically stable and controlled patients selective and superselective embolization is a safe and effective method for the management of renal vascular injury.

Abdominal Injuries↗