beta-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of beta-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of beta-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of beta-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of beta-lapachone was 15.5%. The considerable degradation of beta-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of beta-lapachone may be resulted from the first-pass metabolic degradation of beta-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.
Administration, Intravenous ; Administration, Oral ; Animals ; Biological Availability* ; Chromatography, High Pressure Liquid ; Dosage Forms ; Intestines ; Liver ; Metabolism* ; Pharmacokinetics ; Plasma ; Rats* ; Solubility

The prevalence of unruptured intracranial aneurysm varies between 3.6% and 6%.Aneurysms in the posterior circulation, inaccessible by normothermic surgical clipping and giant aneurysms require direct surgical clipping under hypothermic circulatory arrest for cerebral protection.The authors describe a case of giant basilar aneurysm clipping requiring deep hypothermic total circulatory arrest under total intravenous anesthesia.The patient was a 43-year-old female with a giant aneurysm at the tip of the basilar artery.Total intravenous anesthesia with propofol (average effect site concentration 4 mcg/ml) and remifentanil (average effect site concentration 3 ng/ml) and deep hypothermic total circulatory arrest were performed.Neurophysiologic function was monitored by electroencephalography, and somatosensory and motor evoked potentials. Cardiac and coagulation profiles showed no significant changes. The aneurysm was successfully clipped but the patient expired. Further collations of clinical experiences should enable the identification of an optimal means of anesthetic management during complex cerebrovascular surgery.
Adult ; Anesthesia, Intravenous ; Aneurysm ; Circulatory Arrest, Deep Hypothermia Induced ; Electroencephalography ; Evoked Potentials, Motor ; Female ; Humans ; Intracranial Aneurysm ; Piperidines ; Prevalence ; Propofol ; Surgical Instruments