The kinetics of oxiracetam after single intravenous and oral doses (2000 mg) were investigated in four healthy volunteers. Following intravenous administration, the decline in serum levels showed a prolonged, rapid phase followed by a delayed terminal phase. Mean residence times ranged from 3.9 to 6.5 h. Volumes of distribution ranged from 0.9 to 1.81 X kg-1, whereas clearance values ranged from 100 to 119 ml X h-1 X kg-1 More than 90% of the intravenous dose was recovered unchanged in the urine within 48 h. Oral administration resulted in peak levels within 1-2 h; thereafter, the decline in serum levels showed a pattern similar to that observed after the intravenous dose--almost 50% of the oral dose was excreted in the urine within 6 h. The absolute availability of oral oxiracetam was 75 +/- 7%.

Administration, Oral↗

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Oxiracetam pharmacokinetics following single and multiple dose administration in the elderly.

The kinetics of the nootropic drug oxiracetam was studied in 6 elderly female patients (age range 69-96 years) in good physical condition. After a single oral dose (800 mg), serum oxiracetam levels reached a peak (25 +/- 6 micrograms/ml) within 1-3 h and declined thereafter with a half-life of 3 to 6 h. Eighty-four percent of the administered dose was recovered in urine as unchanged drug within 24 h. During a maintenance regimen (800 b.i.d. at 8 a.m. and 2 p.m.) for 7 days oxiracetam did not show any accumulation in serum, trough serum levels before the morning and afternoon doses being 4.6 +/- 2.3 and 17.0 +/- 8.2 micrograms/ml respectively on day 4 and 5.7 +/- 3.3 and 17.9 +/- 7.7 micrograms/ml respectively on day 7. Comparison with previous pharmacokinetic data obtained in young subjects suggests that the clearance of the drug is lower in the elderly, probably as a result of the physiological decrease in renal function in old age.

Age Factors↗

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Pharmacokinetics of cadralazine in hypertensive patients.

Pharmacokinetics of cadralazine, urinary recovery of its putative active metabolite 3-hydrazino-6-aminopiridazine derivative (ISF 2405) and clinical effects were assessed in a placebo-controlled trial in 8 hypertensive in-patients, after acute oral administration of cadralazine. After a 2-week placebo-washout period, the protocol envisaged two consecutive days of monitoring of blood pressure and heart rate. On the first day a placebo tablet was given (9 am), while on the second day patients received a 30 mg cadralazine tablet in single-blind conditions. Blood and urine samples were obtained during the active drug day until 12 h after administration. Concentration of cadralazine in plasma and urine was detected by a specific HPLC method, while the metabolite ISF 2405 was detected in urine by a GC-MS method. Cadralazine caused gradual and long-lasting pressure decrease, statistically significant in comparison to placebo between 3 and 12 hours from drug intake, accompanied by a significant increase in heart rate. Cadralazine by oral route was promptly absorbed with a mean peak time of 1.3 h. Thereafter it followed a monoexponential decay curve, with a plasma half life of 3.1 h. The relative different bioavailability of oral cadralazine among patients was not correlated with cardiovascular changes. Urine recovery of unchanged drug after 12 h was high, reaching 67.3%, while concentration of metabolite ISF 2405 was about 1/1000 of parent compound.

Adult↗

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Comparative kinetics of oxiracetam in serum and CSF of patients with dementia of Alzheimer type.

The purpose of the study was to determine whether oxiracetam crosses the human blood-brain barrier and to evaluate its comparative kinetics in serum and in cerebro-spinal fluid (CSF). Six DAT patients, undergoing CSF collection for diagnostic purposes, received 2 g oxiracetam daily, by a 60 min i.v. infusion, for 7 days. On the last day, in four patients blood samples were collected at time 0, 30, 60 and 120 min, and lumbar drainage was performed at the end of infusion: at this time mean CSF concentration was 3.5 micrograms/ml, i.e. 4.0% of the serum one, demonstrating that oxiracetam crosses the blood-brain barrier. In two patients, blood samples were collected at time 0, 60, 120 and 240 min, and lumbar drainage was performed 60 min after the end of infusion: at this time mean CSF concentration was 2.8 micrograms/ml, i.e. 5.3% of the serum one, indicating a persistence of oxiracetam within this deep compartment. These results provide the first evidence in humans that oxiracetam penetrates the central nervous system and contribute to the understanding of its long-lasting pharmacodynamic effect in man.

Aged↗

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[Hemorrhage in the Wirsung's duct caused by aneurysm of the splenic artery in chronic pancreatitis].

Two cases of haemorrhage from rupture of a splenic artery aneurysm into the pancreatic duct are reported. Both patients suffered from chronic pancreatitis; when haemorrhage appeared both patients experienced abdominal pain. In one patient the melaena was repetitive, in the other one--with a single episode of melaena - the endoscopy showed fresh blood near the papilla. In both patients ultrasonography and computerized tomography (CT) revealed a cystic mass in the pancreatic tail; CT scan also showed a clear contrast enhancement of these lesions after iodinated medium intravenous bolus. Coeliac arteriography confirmed the presence of two large saccular aneurysmal dilatation of the splenic artery. Both patients underwent a laparotomy: distal pancreatectomy with aneurysm resection and splenectomy were successfully performed.

Aortic Dissection↗

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