Effect of Simultaneous Didanosine Administration on Itraconazole Absorption in Healthy Volunteers

Study Objective . To investigate the effect of simultaneously administered didanosine (ddI) on the absorption of a single dose of itraconazole. Design . Randomized, crossover, unblinded single-dose pharmacokinetic study in healthy volunteers. Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15. Setting . A university medical center. Patients . Seven healthy men and women. Six subjects (86%) completed the study; one was removed due to the development of a rash. Interventions . Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg (two 150-mg tablets) dispersed in 240 ml water. Each regimen was separated by a 2-week washout period. Serum samples were obtained frequently for 12 hours after the dose. Measurements and Main Results . Concentrations of itraconazole were determined using a microbiologic assay. Individual concentrations in serum versus time data were evaluated by linear regression analysis. Peak serum concentration and time to peak were determined by visual inspection of each individual's serum concentration-time curve. A mean ± SD peak serum itraconazole concentration of 0.90 ± 0.30 μg/ml was observed at 3.0 ± 0.7 hours when itraconazole was administered alone, compared with undetectable levels in all patients during therapy with ddI. Conclusions . Simultaneous oral administration of ddI significantly decreases absorption of itraconazole. These drugs should not be administered concurrently.     

Coronary artery fistula presenting as bacterial endocarditis

Coronary artery fistula is often considered to be a benign and rare congenital anomaly. It is usually an incidental finding encountered during routine cardiac catheterization. We report a case of a patient presenting with endocarditis involving a large coronary artery fistula connecting an aneurysmal circumflex coronary artery to the coronary sinus. The diagnosis was initially made by echocardiography and confirmed by cardiac catheterization. In addition, we briefly discuss the literature on management of this coronary anomaly.     

Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke.

We have previously shown that neuregulin-1 (NRG-1) protects neurons from ischemic brain injury if administered before focal stroke. Here, we examined the therapeutic window and functional recovery after NRG-1 treatment in rats subjected to 90 mins of middle cerebral artery occlusion (MCAO) and 24 h of reperfusion. Neuregulin-1 (2.5 ng/kg bolus, 1.25 ng/kg/min infusion) reduced infarct volume by 89.2%+/-41.9% (mean+/-s.d.; n=8; P<0.01) if administered immediately after the onset of reperfusion. Neuroprotection was also evident if NRG-1 was administered 4 h (66.4%+/-52.6%; n=7; P<0.01) and 12 h (57.0%+/-20.8%; n=8; P<0.01) after reperfusion. Neuregulin-1 administration also resulted in a significant improvement of functional neurologic outcome compared with vehicle-treated animals (32.1%+/-5.7%; n=9; P<0.01). The neuroprotective effect of the single administration of NRG-1 was seen as long as 2 weeks after treatment. Neurons labeled with the neurodegeneration marker dye Fluoro-JadeB were observed after MCAO in the cortex, but the numbers were significantly reduced after NRG-1 treatment. These results indicate that NRG-1 is a potent neuroprotective compound with an extended therapeutic window that has practical therapeutic potential in treating individuals after ischemic brain injury.