268 research outputs found
Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks
Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone structure of topotecan, which is in equilibrium with the inactive ringopened hydroxy acid, is essential for this activity. The open form predominates at physiological pH. We performed a pharmacokinetic, study as part of a phase I study in patients with various types of soli
The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor.
Topoisomerase I inhibitors are new compounds of interest for cancer chemotherapy. We performed a study with GI147211, a new semisynthetic camptothecin analogue, to determine the absolute bioavailability of the drug given orally. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard forms of therapy were eligible for the study. GI147211 was given orally on day 1 and as a 30-min infusion daily on days 2-5. The treatment course was repeated every 3 weeks. In subsequent patient cohorts, the dose of the oral formulation was escalated from 1.5 mg m(-2) to 6.0 mg m(-2); the dose for i.v. administration was fixed at 1.2 mg m(-2). Plasma pharmacokinetics was performed on day 1 and 2 of the first course and on day 1 of the second course using a validated high-performance liquid chromatographic assay. Nineteen patients were entered into the study; one patient was not evaluable because the treatment course was stopped prematurely. Eighteen patients received a total of 47 treatment courses. The absolute bioavailability of GI147211 averaged 1.3 +/- 5.2%. Drug appeared quickly in plasma with a median Tmax at 0.5 h. Fasting or fed state had no significant influence on the bioavailability of GI147211. The terminal half-life after administration of oral GI147211 was 6.85 +/- 3.13 h, similar to the half-life after intravenous administration. The major toxicities were neutropenia and thrombocytopenia. Nadirs for neutropenia and thrombocytopenia occurred on day 8 and day 15 respectively. Other toxicities predominantly consisted of mild and infrequent nausea and vomiting, and fatigue. The oral administration of the drug is well tolerated. Oral administration of topoisomerase I inhibitor GI147211 results in a low bioavailability with relatively wide interpatient variation. The intravenous route of administration is advised for further development of this promising topoisomerase I inhibitor
Experimental determination of the complete spin structure for anti-proton + proton -> anti-\Lambda + \Lambda at anti-proton beam momentum of 1.637 GeV/c
The reaction anti-proton + proton -> anti-\Lambda + \Lambda -> anti-proton +
\pi^+ + proton + \pi^- has been measured with high statistics at anti-proton
beam momentum of 1.637 GeV/c. The use of a transversely-polarized frozen-spin
target combined with the self-analyzing property of \Lambda/anti-\Lambda decay
allows access to unprecedented information on the spin structure of the
interaction. The most general spin-scattering matrix can be written in terms of
eleven real parameters for each bin of scattering angle, each of these
parameters is determined with reasonable precision. From these results all
conceivable spin-correlations are determined with inherent self-consistency.
Good agreement is found with the few previously existing measurements of spin
observables in anti-proton + proton -> anti-\Lambda + \Lambda near this energy.
Existing theoretical models do not give good predictions for those
spin-observables that had not been previously measured.Comment: To be published in Phys. Rev. C. Tables of results (i.e. Ref. 24) are
available at http://www-meg.phys.cmu.edu/~bquinn/ps185_pub/results.tab 24
pages, 16 figure
Measurement of Spin Transfer Observables in Antiproton-Proton -> Antilambda-Lambda at 1.637 GeV/c
Spin transfer observables for the strangeness-production reaction
Antiproton-Proton -> Antilambda-Lambda have been measured by the PS185
collaboration using a transversely-polarized frozen-spin target with an
antiproton beam momentum of 1.637 GeV/c at the Low Energy Antiproton Ring at
CERN. This measurement investigates observables for which current models of the
reaction near threshold make significantly differing predictions. Those models
are in good agreement with existing measurements performed with unpolarized
particles in the initial state. Theoretical attention has focused on the fact
that these models produce conflicting predictions for the spin-transfer
observables D_{nn} and K_{nn}, which are measurable only with polarized target
or beam. Results presented here for D_{nn} and K_{nn} are found to be in
disagreement with predictions from existing models. These results also
underscore the importance of singlet-state production at backward angles, while
current models predict complete or near-complete triplet-state dominance.Comment: 5 pages, 3 figure
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