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Formation and Antitumor Activity of PNU-159682, A Major Metabolite of Nemorubicin in Human Liver Microsomes
CYP3A4, the major CYP in human liver, converts MMDX to a more cytotoxic metabolite, PNU-159682, which retains antitumor activity in vivo.
Full efficacy with no CNS side-effects: unachievable panacea or reality? DMPK considerations in design of drugs with limited brain penetration
Two in-house chemistry programmes resulted in highly orally bioavailable low CNS penetrant compounds in preclinical species by increasing polar surface area and utilising active transport to exclude compounds from the brain.
Single- and multiple-dose disposition kinetics of sunitinib malate, a multitargeted receptor tyrosine kinase inhibitor: comparative plasma kinetics in non-clinical species
Sunitinib exhibited advantageous pharmacokinetic and dispositional properties in non-clinical species, translating into favorable properties in humans.
Accelerated extractable studies of borosilicate glass containers.
- S. J. Borchert, M. M. Ryan, R. L. Davison, W. Speed
- EngineeringJournal of parenteral science and technology : a…
- 1 March 1989
The procedure, which is very similar to a protocol developed by a PDA Task Force, includes the monitoring of Si, Na, K, Al, Ba, Ca, Mg, Fe, and Zn in the extracts as well as measurements of pH change and total extractables.
Assessment of normal and tumor tissue uptake of MAG-CPT, a polymer-bound prodrug of camptothecin, in patients undergoing elective surgery for colorectal carcinoma
Delivery of CPT to the target tumor tissue is achievable by means of the MAG-CPT polymer-bound delivery system, with the equilibrium between plasma and tumor tissue concentrations of released CPT being established within 24 h after dosing.
Alkylpyrazines in ponerine ants: Their presence in three genera, and caste specific behavioural responses to them in Odontomachus troglodytes
Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)
The objectives of this study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment.
The development and validation of a high performance liquid chromatography (HPLC)/tandem mass spectrometry assay for fenticonazole in human plasma and comparison with an HPLC-UV method.
- W. Speed, J. Long, R. J. Simmonds, T. Enos
- ChemistryRapid communications in mass spectrometry : RCM
A method is described for the determination of fenticonazole in human female plasma. The method utilizes high performance liquid chromatography coupled to atmospheric pressure positive-ion chemical…
Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity.
A novel series of amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity and compound 26 shows high levels of in vivo efficacy against Leishmania infantum, thus demonstrating proof of concept for this series.
The use of liquid chromatography/thermospray mass spectrometry with on-line ultraviolet diode array and radiochemical detection: characterization of the putative metabolites of U-78875 in female rat…
On-line radiochemical and UV diode array detection greatly facilitates the TSP/LC/MS characterization of metabolites from studies using radiolabelled drugs.