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At least 289 records · Page 16Linked to original sources
PubMed1993

Pharmacokinetics of 4-hydroxyandrostenedione in man after intramuscular injection of different formulations and the effect of this drug on plasma aromatizable androgens and 17beta-estradiol concentrations.

Pharmacokinetics of 4-hydroxyandrostenedione (4-OHA), a potent aromatase inhibitor under investigation for treatment of postmenopausal breast cancer, were studied using two formulations with different particle sizes of 4.2 and 8.0 microm, respectively. A single 250 mg dose of 4-OHA of each of the two formulations was administered in two different periods to six healthy male volunteers and blood samples were collected for up to 14 days. 4-OHA plasma levels were determined using the isotope dilution mass spectrometry method. Comparison of the pharmacokinetic profiles of the two formulations did not show any statistically significant difference, even though the 4.2 microm particle size gave apparently higher levels at 24 h. Using this formulation, the effects of 4-OHA on the plasma levels of aromatizable androgens (testosterone and androstenedione) and 17beta-estradiol were studied. An isotope dilution mass spectrometry method was developed for the simultaneous quantitative determination of these steroids in human plasma. The analysis of plasma samples showed a significant reduction of plasma estradiol concentrations (50%) which coincided with the maximum concentration peak of the inhibitor, whereas no significant changes in androgen levels were observed.

Androgens↗
PubMed2005

Vascular endothelial growth factor gene therapy with intramuscular injections of plasmid DNA enhances the survival of random pattern flaps in a rat model.

The objective of this study was to determine the effects of the naked plasmid DNA encoding vascular endothelial growth factor (VEGF) on the survival of random flaps on rats. Thirty Sprague-Dawley rats whose random flaps were elevated on the back were randomised into three groups of 10 animals each. In the experimental group, the naked plasmid DNA encoding VEGF was injected directly into the panniculus carnosus of the flap. In the two control groups, either control plasmid DNA or physiologic saline was injected. After 7 days, the flaps were evaluated with the following devices: RT-PCR for the expression of VEGF gene, immunohistochemistry for the expression of VEGF protein, histology for vascular density, single photon emission computerised tomography for RBC in the flap, and image analysis for flap survival area. Notably increased expressions of VEGF mRNA and VEGF protein were found in the treatment group. Vascular density was markedly more increased in the treatment group than those in the two control groups (P < 0.01). Compared with the two control groups, the flap treated with VEGF plasmid DNA showed a more significantly enhanced tissue viability: 87 +/- 5 versus 47 +/- 6% for the control plasmid DNA group and 46 +/- 5% for the saline group (P < 0.01). Our results indicated that the VEGF gene therapy was able to enhance the survival of random pattern flaps by inducing angiogenesis.

Animals↗
PubMed2005

Pharmacokinetics (PK) of S/D treated anti-D immunoglobulin after intramuscular injection in healthy volunteers: gender differences in PK.

The aim of this study was to investigate the pharmacokinetic profile of the new solvent/detergent (S/D) formulation of an anti-D IgG preparation, and to evaluate gender differences. RhD-negative subjects (m/f=10/8) received a single i.m. injection of 250 microg anti-D (Partobulin SDF). There was a rapid increase in median anti-D titers over the first 2 days, followed by a plateau from days 2-7. Interestingly, women had a higher maximum concentration (Cmax) of anti-D and a lower volume of distribution at steady state (Vss) than men. The half-life calculated in this study was 23 days. Thus, results are comparable to published data of the non-S/D treated predecessor product. Because of the observed gender differences in the pharmacokinetics we recommend to pursue the evaluation of sex differences in the pharmacokinetics of other antibodies during early phase drug development.

Female↗
PubMed2000

Behavioral responses to intramuscular injections of prostaglandin F(2 alpha) in female pigs.

This study investigated the effect of different doses (0-1.25 mg/kg IM) of prostaglandin (PG) F(2 alpha) on the behavior of female pigs (Sus scrofa). Six-month-old cyclic nulliparous sows (gilts) were housed and tested individually in strawed pens (2.8 x 1.7 m). All doses of PGF(2)alpha induced rooting, pawing at the ground, and gathering straw. In the hour following treatment the frequency of pawing increased with increasing dose to reach a maximum level with the highest dose given. The frequency to gather straw was highest in pigs treated with the lowest dose (0.008 mg/kg). The frequency of oronasal contact with the floor and pen walls was unaffected by dose. Scratching, locomotion, and changes in body posture were highest following treatment with the three highest doses of PGF(2 alpha). Many of the behaviors observed following PGF(2 alpha) treatment are characteristic of prepartum nesting behavior in pregnant sows. We conclude that two key components of maternal nest-building behavior, pawing, and gathering straw, are affected differentially by different doses of PGF(2 alpha). The implications of these results on the mechanisms underlying maternal nest building in pigs are discussed.

Animals↗