PubMed Health⌕ Search

Biomedical subjects

P Leese

Publications and source records attributed to P Leese.

8 recordsLinked to original sources
PubMed1997

The pharmacokinetic and pharmacodynamic interaction between zileuton and terfenadine.

OBJECTIVES: The effects of zileuton on terfenadine pharmacokinetics, and the effects of terfenadine alone and the combination on the duration of the QTc interval and the morphology of the TU complex were examined. METHODS: The study was double-blind, randomized, placebo-controlled, two period cross-over in 16 healthy volunteers. During each period, subjects received 60 mg of terfenadine every 12 h on days 1 to 7 and 600 mg of either zileuton or placebo for zileuton every 6 h on days 1 to 10. Blood samples were obtained on days 7 to 10 and serial ECGs were performed on days -1 and 7 in both periods. RESULTS: The combination of zileuton and terfenadine was well tolerated. Coadministration of zileuton with terfenadine resulted in a significant increase in the mean AUC and Cmax of terfenadine by approximately 35% and the mean AUC and Cmax of carboxyterfenadine by approximately 15%. The maximum concentration of terfenadine observed in the study was 9.6 ng.ml-1. The addition of zileuton to terfenadine did not result in significant changes in the evaluated ECG-recordings (QTc interval and morphology of TU complex). The difference in means for both maximum and average QTc interval was very small (< or = 2.3 ms), and there were no clinically significant changes in individual values. CONCLUSIONS: The relatively small pharmacokinetic effect of zileuton on terfenadine metabolism, with no change in the QTc interval, is unlikely to be of clinical significance. The interaction is minimal in comparison to the background variability of the population.

Adult↗
PubMed1997

Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers.

Tolcapone (Ro 40-7592) is a novel inhibitor of catechol-O-methyltransferase that is being developed for clinical use in the treatment of Parkinson's disease as add-on therapy to a combination of levodopa and a peripheral amino acid decarboxylase inhibitor (benserazide or carbidopa). The current single-blind, randomized study was designed to evaluate the effect of tolcapone compared with placebo on plasma levodopa concentrations in healthy volunteers concomitantly receiving 25 mg of carbidopa and 100 mg of levodopa (Sinemet 25-100) and to assess the tolerability and safety of this combination. Placebo or tolcapone at doses of 5, 10, 25, 50, 100, 200, 400, and 800 mg was coadministered orally with Sinemet 25-100. Each dose was tested in a crossover fashion in a new group of six participants who each received active drug on one occasion and placebo on the other. Tolcapone increased the area under the plasma concentration-time curve and half-life of levodopa approximately twofold, without appreciably increasing the peak concentration. The maximum effect on levodopa half-life was observed with the 200-mg dose. Adverse effects were minor at all doses.

Adolescent↗
PubMed1994

Preclinical and clinical studies on lymph node imaging using perflubron emulsion.

A perflubron emulsion is being developed as a contrast agent to enhance lymph nodes on computed tomography (CT) images. The emulsion is administered by percutaneous injection into the drainage field of the lymph nodes to be imaged. A series of preclinical studies was conducted to investigate the efficacy of the perflubron emulsion for enhancement of lymph nodes on CT images. The effects of dose (0.10 to 0.50 mL), application of massage, and route of administration were investigated in healthy New Zealand white rabbits. Results of these studies demonstrated that doses as low as 0.15 mL were efficacious for consistent enhancement of axillary lymph nodes on CT images after subcutaneous injections in the forepaw. Application of massage to the injection site decreased the time for maximum nodal enhancement from approximately 7 days to 2 days postinjection. A pilot study conducted in 18 healthy, male volunteers indicated dose-related enhancement of axillary lymph nodes on CT images following subcutaneous injections of the emulsion in the hand. Other than mild, transient injection-site discomfort, no clinically significant side effects were observed. These data demonstrate that the perflubron emulsion is safe and can enhance axillary lymph nodes on CT images following injections in the hand.

Analysis of Variance↗
PubMed1992

Comparison of the effects of etodolac SR and naproxen on gastro-intestinal blood loss.

A single-blind, open-label controlled study was carried out in 30 healthy male volunteers to compare gastro-intestinal blood loss before, during and after treatment with a new, sustained-release formulation of the non-steroidal anti-inflammatory agent etodolac (etodolac SR) or with naproxen. Subjects remained at the study centre for 21 days and received placebo twice daily from Days 1 to 7 after which they were assigned at random to receive etodolac SR either as a single 600 mg or 1200 mg daily dose or naproxen (500 mg twice daily) for 7 days and then placebo again until the end of the study. There were 10 subjects in each of the three treatment groups. Gastro-intestinal blood loss was measured by the 51Cr-tagged erythrocyte method and was averaged for Days 4 to 7 (pre-treatment baseline), Days 11 to 14 (treatment period), and Days 17 to 20 (post-treatment period). The mean daily gastro-intestinal blood loss during the treatment period was significantly greater for the naproxen-treated group (1.20 ml/day) than for the 600 mg etodolac SR group (0.38 ml/day) and the 1200 mg etodolac SR group (0.45 ml/day). These results show that etodolac SR in doses of 600 mg and 1200 mg/day causes significantly less gastro-intestinal blood loss than does naproxen 500 mg twice daily.

Adult↗
PubMed1990

An evaluation of the biological response to Fraxiparine, (a low molecular weight heparin) in the healthy individual.

The tolerance of a low molecular weight heparin (Fraxiparine, Choay, Paris, France) in normal individuals was determined using a two part investigation. Study 1 consisted of administering escalating doses of Fraxiparine in a single blinded, placebo controlled, rising dose tolerance evaluation. The daily doses tested were 3750 U AXA IC, 7500 U AXa IC, 11250 U AXa IC, 15000 U AXa IC, and 22500 U AXa IC Fraxiparine subcutaneously for 5 consecutive days. In study 2, we compared the tolerance of unfractionated heparin (UH) administered as 5000 IU every 8 hours, to that of 7500 U AXa IC/day or 15000 U AXa IC/day of Fraxiparine administered once daily. Our results indicated very good tolerance to this low molecular weight heparin (LMWH) at doses up to and including 22500 U AXa IC/day. We observed significantly elevated increases in transaminases following LMWH administration. In our second study we observed that the increase in serum transaminases seen after 15000 U AXa IC/day Fraxiparine was without significant difference from that observed following UH (5000 IU every 8 hours). AXa examination revealed an accumulation of AXa effect after 5 days of administration at doses greater than 15000 U AXa IC, and there was good correlation between AXa and APTT at Fraxiparine doses greater than 15000 U AXa IC/day. No thrombocytopenia was associated with Fraxiparine. We conclude that Fraxiparine is relatively well tolerated and shows accumulation after daily dosing with greater than 15000 U AXa IC.

Adult↗