the circadian variation of the toxicity and nociceptive activity of aminophylline as an important methylxanthine was studied in mice. the animals were housed under controlled light-dark cycles for at least 2 weeks. acute toxicity was determined by ld50. hot-plate test was used for determination of thermal pain threshold. doses of 200, 250, 280 and 340 mg/kg of aminophylline were injected intrap...

PURPOSE Inhibition of the enzyme cyclooxygenase with celecoxib is cytotoxic in a variety of solid tumor cell lines. Previous work has shown that by charting circadian rhythms, it has been possible to find optimal times to deliver a dose of drug, such that it is most efficacious in killing cancer cells and least harmful to normal tissues. Therefore, we examined the time dependence of toxicity (c...

The influence of dosing time on the embryotoxicity of sodium valproate (valproic acid, VPA) was investigated in ICR mice under a light-dark (12:12) cycle. A significant circadian rhythm was shown for VPA-induced embryotoxicity, with the highest value at 1700 and the lowest at 0100. A similar pattern of rhythm was also shown for VPA-induced toxicity in pregnant and nonpregnant mice. No significa...

The mechanisms underlying the circadian rhythm of the toxicity induced by irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) were investigated from the viewpoint of the sensitivity of living organisms and the pharmacokinetics of the drug. ICR male mice were housed under standardized light-dark cycle conditions (lights on at 0700, off at 1900) wi...