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Dr James Best, General Practitioner A Prof Nick Buckley, Clinical Pharmacologist, The Canberra Hospital Ms Jan Donovan, Consumer Dr John Dowden, Medical Editor, Australian Prescriber Ms Simone Rossi, Managing Editor, Australian Medicines Handbook Ms Susan Parker, Head of Medical Affairs, Pfizer Australia Any correspondence regarding content should be directed to NPS. Declarations of interest have been sought from all reviewers.
Single-Dose Rexinoid Suppresses Serum Thyrotropin 06-0696 V2 Results Six subjects 5 females, 1 male, age 24 53 years ; completed the study. Table 1 shows individual values for screening TSH, height, weight, body surface area, and bexarotene dosing for each of these subjects. The average baseline TSH + SEM ; was 1.47 + 0.11 mU L and 1.43 + 0.08 mU L for the placebo and bexarotene arms of the study, respectively. There was no effect of bexarotene alone on serum TSH F 4.4; p 0.089 ; . However, there was an interaction effect of bexarotene and time; single dose bexarotene 400 mg m2 ; significantly suppressed serum TSH F 6.9; p 0.001 ; . Compared to placebo, levels of TSH were significantly lowered at 12 hours p 0.043 the nadir of 0.32 + 0.02 mU L was seen at 24 hours p 0.001 ; , and levels remained lower at 48 hours p 0.001 ; Figure 1 ; . Individual subject TSH values at baseline and 24 hours are shown in Figure 2. All six subjects had lower serum TSH levels after bexarotene administration; 5 of 6 subjects had TSH below the lower reference range 0.5 mU L ; . Serum prolactin levels were not significantly affected by bexarotene at 24 hours Figure 3 ; . Mean prolactin concentrations before and 24 hours after bexarotene administration were 10.3 + 0.6 and 9.3 + 0.6 ng mL, while prolactin levels before and 24 hours after placebo were 10.0 + 0.6 and 13.7 + 1.1 ng mL. One study suggested that the circadian variation in endogenous cortisol secretion may affect TSH levels 18 ; . Treatment with bexarotene had no significant effect of serum cortisol levels in these subjects Figure 4 ; . Single-dose bexarotene significantly affected free T4 index Figure 5A, F 2.4; p 0.029 for drug time interaction ; and free T3 index Figure 5B, F 3.4; p 0.004 ; over time 48 hours ; . The drug effect was significant at 48 hours for free T4 index p 0.027 ; , and at 12 p 0.002 ; , 24 p 0.001 ; and 48 hours p 0.001 ; for free T3 index. There was a trend toward a.
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This is the first report on the detection of BPDEDNA adducts in human preimplantation embryos. Furthermore, we also showed a relationship between parental smoking and these adducts. Using three measures of immunostaining intensity, we showed that embryos of smoking couples have, on average, higher levels of reactivity to the monoclonal antibody than do embryos of non-smoking couples. There was a 3.6-fold increase for the mean score of immunostaining intensity. These results indicate that parental smoking, through gametic transmission of modified DNA to the embryo, results in detectable BPDE DNA adducts in the embryo. Our approach using immunoperoxidase for monitoring exposure to environmental pollutants in cigarette smoke is therefore useful when relatively small numbers of cells are available Hsu et al., 1997; Zenzes et al., 1998 ; , as in the present study. 128.
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4, no 2, pages 180-188 doi: 1 1586 1473714 ; bexarotene: a clinical review len t farol , kenneth b hymes bexarotene targretin ® , ligand pharmaceuticals inc ; is a synthetic retinoid analog with specific affinity for the retinoid x receptor and belongs to a group of compounds called rexinoids.
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Bexarotene: health search results from the invisible web : : overview : : precautions : : side effects : : further reading search results 1 21 2008 generic & brand name : source: rxlist ; brand name : targretin generic name : bexarotene overview source: drugdigest ; bexarotene targretin ; is a medicine similar to vitamin bexarotene is used to treat certain types of cancer including cutaneous t cell lymphoma mycosis fungoides ; and breast cancer and bioflavonoids.
Belleville news-democrat vitamin a-like compound fights lung cancer jan 24, 2006 the compound bexarotene put the brakes on lung tumors in mice genetically engineered to be susceptible to the cancer, say researchers at the washington.
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Figure 2. Just over 90% of all persons committed to prison in 2001 were male. Over 19% were aged under 21 years and 14.5% over 40 years of age.
Discussion In general, the qualitative metabolite profiles were similar in rat, dog, and human as demonstrated in the representative chromatograms shown in Figs. 2 to 5, 7 and 11 to 12, respectively. Consistent with findings for the rat Shirley et al., 1997 ; , the significant routes of metabolism of bexarotene in the dog and human were oxidation at C-6 and C-7 and glucuronidation, with oxidation at C-6 predominating over that at C-7 in all three species. Metabolite profiles for bexarotene in rat liver microsomes were consistent with those in rat liver slices. Although hydroxylated bexarotene was detected previously in the bile of bexarotene-treated rats, the mass spectral method used was not quantitative Shirley et al., 1997 ; , and the small amounts present were not detectable by UV absorbance. In the present study, other than the absence of phase I metabolites, the metabolite profiles in the bile of rats and a dog were qualitatively similar to the profiles in the liver slice model. The presence of the oxidized metabolites in plasma but not bile suggests selective transport of these compounds into the bloodstream, probably due to the action of transporter enzymes. A species difference in biliary metabolite profile existed in that bexarotene acyl glucuronide was the predominant metabolite in rat, while in dog the major metabolite was hydroxylated bexarotene acyl glucuronide. This is opposite the relationship observed in liver slices, in which the major glucuronides for rat were of oxidative metabolites while for the dog, the major glucuronide was that of the parent compound. Since the primary route of bexarotene excretion is hepatobiliary in rats and dogs2, glucuronidation is likely the primary route of bexarotene metabolism in these species. 6 7-Hydroxy-bexarotene and, to a lesser extent, 6 7-oxo-bexarotene appeared to be the major drug-related species in plasma from rats, dogs, and humans having received bexarotene. For both the hydroxy and oxo metabolites, the C-6 isomer was predominant. Therefore, 6-hydroxy-bexarotene was the major circulating metabolite in all three species. A difference in circulating metabolite levels was observed between humans and the other species; while in the rat and dog the parent was more abundant than either metabolite, in humans, 6 7-hydroxy-bexarotene was more abundant than parent and the abundance of 6 7-oxo-bexarotene was less than or equivalent to that of parent. This difference may be related to involvement of different cytochrome P450 isozymes in the different species. While CYP3A has been demonstrated to be involved in the oxidation of bexarotene in microsomes from both rat and human livers, CYP2B was also implicated in rat and CYP2C9 and CYP2C19 may be involved in human Hein et al., 1996 ; . Synthetic bexarotene metabolites exhibited in vitro activity at retinoid receptors that was much reduced relative to parent, albeit each and bleomycin.
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She initially responded to bexarotene Targretin; Ligand Pharmaceuticals Inc, San Diego, Calif ; 150 mg d ; and interferonalfa 1.8 106 U, 3timesweekly ; .However, within 2 months of initiating these therapies, her disease had progressed rapidly with an increase in size, number, and degree of infiltration of the lesions and worsening of her constitutional symptoms with increased fatigue and low-grade fevers. She was prescribed prednisone 15 mg d orally and boniva.
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