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Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of(More)
The present study tested the hypothesis that the experimental antineoplastic imidazotetrazinone temozolomide degrades in the biophase to 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) and exerts its cytotoxicity via this species. MTIC is a metabolite of the antimelanoma agent dacarbazine and is thought to be responsible for the antineoplastic(More)
Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the(More)
Modified early warning scoring (MEWS) uses abnormalities in routine observations to identify patients at risk of critical illness. Nurses recorded scores at or above the medical response score of 3 on a hospital clinical information system during the first year of introducing MEWS to 10 wards in a university hospital. A total of 619 triggers were recorded(More)
The authors determined plasma levels of metoprolol, a widely used beta-adrenoceptor blocker, following oral administration of 100 mg to 23 women. 1/2 of this group were taking a combined estrogen-ethinyl estradiol low dose oral contraceptive (OC). Blood samples were taken before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dosing. The volunteers(More)
1 Plasma concentrations of metoprolol and a pharmacologically active metabolite, H119/66, have been measured in young and elderly volunteers after a single dose of 100 mg metoprolol tartrate and after repeated administrated over a period of 1 week. Whilst concentrations of metoprolol are similar in each group, concentrations of H119/66 are approximately(More)
The in vitro cytotoxicity, stability, and metabolism of the 8-(N,N-dimethylcarboxamide) and 8-(N-methylcarboxamide) analogues of the experimental antitumor drug mitozolomide have been investigated in conjunction with their in vivo murine pharmacokinetics and metabolism. When tested against the TLX5 lymphoma in vitro the ID50 values for dimethylmitozolomide,(More)
Plasma concentrations of three beta-adrenoceptor blocking agents, propranolol, oxprenolol, and metoprolol, have been measured over 24 h after a single oral dose in patients with active inflammatory disease, and in healthy subjects. After propranolol administration, peak plasma concentrations were approximately seven times higher in the patients; they(More)
Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young health volunteers. In order to assessed the inter- and intra-subject variability the following pharmacokinetic parameters were compared: AUC0(24), Cmax, tmax and t 1/2. The smallest variation in inter-subject(More)