Precipitation in and supersaturation of contents of the upper small intestine after administration of two weak bases to fasted adults.

PURPOSE: To evaluate precipitation in and supersaturation of intestinal contents after administration of pharmacologically relevant doses of dipyridamole and ketoconazole to 12 healthy adults. METHODS: On two separate days each subject was administered in stomach 240 ml aqueous solutions of two dipyridamole doses (30/90 mg) and two ketoconazole doses (100/300 mg). Physicochemical characteristics, total drug content, and drug concentration were measured in individual intestinal contents (≤7 ml) aspirated at specific times post-dosing. Drug concentration after incubation (37°C/48 h) and equilibrium solubility were measured. Precipitate crystallinity was evaluated by x-ray powder diffraction. RESULTS: Precipitated fraction was minimal (dipyridamole, ≤7%) or limited (ketoconazole, ≤16%). Ketoconazole precipitates were mostly amorphous. Depending on dose, intestinal contents with pH > 3.6 were supersaturated with dipyridamole up to 10 and 30 min and with ketoconazole up to 30 and 50 min post-administration. Intestinal contents with pH > 5 and concentration of micellar components <5 mM were supersaturated with ketoconazole or dipyridamole, but precipitated fraction was significant only for ketoconazole. After incubation, crystalline precipitates were found in almost all samples. Slow precipitation of base and/or precipitation of other phases account for this observation. CONCLUSIONS: Intralumenal precipitation of weakly alkaline, lipophilic, high permeability drugs may not be substantial. Estimating intestinal supersaturation in regard to free base is inadequate as other phases may precipitate.

Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies.

PURPOSE: This study was conducted to compare the luminal composition of the upper gastrointestinal tract in the fasted and fed states in humans, with a view toward designing in vitro studies to explain/predict food effects on dosage form performance. METHODS: Twenty healthy human subjects received 250 mL water or 500 mL Ensure plus (a complete nutrient drink) through a nasogastric tube and samples were aspirated from the gastric antrum or duodenum for a period up to 3.5 h, depending on location/fluid combination. Samples were analyzed for polyethylene glycol, pH, buffer capacity, osmolality, surface tension, pepsin, total carbohydrates, total protein content, and bile salts. RESULTS: Following Ensure plus administration, gastric pH was elevated, buffer capacity ranged from 14 to 28 mmoL L-1 DeltapH-1 (vs. 7-18 mmol L-1 DeltapH-1), contents were hyperosmolar, gastric pepsin levels doubled, and surface tension was 30% lower than after administration of water. Post- and preprandial duodenal pH values were initially similar, but slowly decreased to 5.2 postprandially, whereas buffer capacity increased from 5.6 mmol L-1 DeltapH-1 (fasted) to 18-30 mmol L-1 DeltapH-1 (p<0.05). Postprandial surface tension in the duodenum decreased by >30%, bile salt levels were two to four times higher, luminal contents were hyperosmotic, and the presence of peptides and sugars was confirmed. CONCLUSIONS: This work shows that, in addition to already well characterized parameters (e.g., pH, and bile salt levels), significant differences in buffer capacity, surface tension, osmolality, and food components are observed pre-/postprandially. These differences should be reflected in test media to predict food effects on intralumenal performance of dosage forms.

Freehand two-step CT-guided brain tumor biopsy: a fast and effective interventional procedure in selected patients.

PURPOSE: To evaluate the efficacy and safety of CT-guided needle biopsy of brain lesions without a stereotactic device, and to determine the best possible indications for this technique. METHODS: From February 2001 to February 2004, 20 patients (12 men, 8 women; age 61-82 years) underwent CT-guided brain lesion biopsy. The procedure started with a brain CT scan for lesion localization and for selection of the inlet for needle insertion. The patient was then transported to the operating room where cranioanatrisis was performed. Subsequently, the biopsy was performed under CT guidance using a 14G brain biopsy needle with a blind smooth end and lateral holes. At the end of the biopsy, the field was checked for possible complications with a CT scan. RESULTS: Histopathologic results were: brain tumor in 16 patients (80%), inflammatory process in 3 (15%), and no conclusive diagnosis in 1 (5%). A repeat of the process was required in 2 patients. A minor complication of local hematoma was found in 1 patient (5%). There were no deaths or other serious complications. CONCLUSION: CT-guided biopsy is a reliable method for histopathologic diagnosis of brain lesions in selected cases. It is a simple, fast, effective, low-cost procedure with minimal complications, indicated especially for superficial and large tumors.

Percutaneous CT-guided interventional procedures in musculoskeletal system (our experience).

Percutaneous interventional procedures include a broad spectrum of minimal invasive techniques, which are a useful diagnostic and therapeutic tool. In this study we present our experience in CT-guided percutaneous musculoskeletal biopsies, drainages of musculoskeletal abscesses, facet and sacroiliac joint injection and radiofrequency thermal ablation of painful metastases or osteoid osteomas.

Osseous Kaposi sarcoma in an HIV-positive patient.

A case of osseous Kaposi sarcoma in a 35-year-old man is described. The patient (HIV-positive for 8 years) suffered from cutaneous Kaposi sarcoma and presented with right-sided chest pain. He underwent a chest CT scan that revealed three osteolytic lesions involving rib and vertebra with large soft tissue masses, without cutaneous lesions at these sites. CT-guided core needle biopsy led to a histological diagnosis of Kaposi sarcoma.