A bioavailability study of two preparations of tamoxifen after single doses

The bioavailability of two different tablet formulations of tamoxifen was studied in twelve healthy male volunteers. Two tablets, each of 10 mg, of both preparations were administered orally at intervals of two weeks in a randomized cross-over design. Samples of blood for tamoxifen measurement were taken for up to 48 h following administration. Tamoxifen was measured by an HPLC method sensitive to 2.0 ng ml(-1). The area under the concentration-time curve was similar for both preparations. The study, therefore, did not demonstrate any differences between the bioavailability of the two preparations of tamoxifen.     

Adjunctive magnesium sulfate infusion does not alter metabolic changes associated with ritodrine tocolysis

Magnesium sulfate, an agent whose cellular actions might cause metabolic disturbances, has been used concomitantly with ritodrine hydrochloride for preterm labor tocolysis. Although the profound metabolic effects of beta-adrenergic agents have been well described, the possibility that adjunctive magnesium might cause further or unexpected alterations in maternal metabolic parameters has not been fully evaluated. To investigate this question, we prospectively randomized patients, in a blinded fashion, to receive ritodrine plus placebo or ritodrine plus adjunctive magnesium sulfate for preterm labor tocolysis. Serial measurements of potassium, glucose, blood urea nitrogen, and hematocrit were obtained and compared between tocolytic treatment groups. The metabolic changes found were similar in each group and appear to result predominantly from beta-adrenergic stimulation with no apparent perturbations caused by the direct cellular actions of magnesium sulfate. From the metabolic standpoint, it appears that the clinician may use adjunctive magnesium sulfate without fear of accentuating or obscuring the expected beta-adrenergic-induced alterations in the above-mentioned maternal metabolic parameters.     

Psychosocial Correlates of Monocyte Activation and HIV Persistence in Methamphetamine Users

This cross-sectional study investigated the associations of psychosocial factors relevant to recovery from substance use disorders with monocyte activation and HIV persistence in a sample of 84 HIV-positive, methamphetamine-using sexual minority men with undetectable HIV viral load (<40 copies/mL). We examined if psychosocial factors were associated with decreased soluble CD14 (sCD14) and lower proviral HIV DNA. Multiple linear regression models adjusted for age, anti-retroviral therapy regimen, and CD4+ T-cell count. Time on ART was also included in models examining proviral HIV DNA. Greater self-efficacy for managing methamphetamine triggers and higher social support for abstinence were independently associated with lower sCD14. Greater social support for abstinence was also independently associated with lower proviral HIV DNA. Psychosocial factors relevant to recovery from substance use disorders are associated with lower monocyte activation and decreased proviral HIV DNA. Findings underscore the need for longitudinal research to identify plausible mechanisms linking psychosocial factors and substance use with biological processes relevant to HIV pathogenesis.

     

A randomised comparison of the effects of oral versus transdermal 17beta-oestradiol, each combined with sequential oral norethisterone acetate, on serum lipoprotein levels.

OBJECTIVE: To investigate the effects of oral versus transdermal 17beta-oestradiol, given in both cases with sequential addition of oral norethisterone acetate, on serum lipid and lipoprotein levels in postmenopausal women. DESIGN: Open, randomised, parallel groups study. SETTING: University Clinical Research Group. POPULATION: Sixty-four postmenopausal women with climacteric complaints who were otherwise healthy were screened. Of these, 58 fulfilled the entry criteria. METHODS: Fifty-eight postmenopausal women were randomised to receive either oral 17beta-oestradiol/oestriol (Trisequens) or transdermal 17beta-oestradiol (Estrapak) together with cyclical addition of norethisterone acetate for 48 weeks. MAIN OUTCOME MEASURES: Serum levels of total cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL), very low density lipoproteins (VLDL), apolipoproteins, and lipoprotein(a) at baseline, and after 46 weeks (oestrogen-alone phase), and 48 weeks (oestrogen-progestogen phase) of treatment. RESULTS: Oral oestradiol therapy did not affect serum total cholesterol levels during the oestrogen-alone phase, but during the combined phase there was a 5% fall (P < 0.05) due to a 7% decrease in LDL cholesterol levels (P < 0.01). Oral therapy also increased serum triglyceride levels by 9.4% during the oestrogen-alone phase (P < 0.05). During the combined phase of transdermal therapy, there was a 19% fall in serum triglyceride levels (P < 0.05) and a 6% fall in HDL levels (P < 0.05). Oral oestradiol reduced lipoprotein(a) levels by 31% during the oestrogen-alone phase and by 37% with norethisterone acetate addition (P < 0.05). Transdermal therapy had no significant effect on lipoprotein(a). CONCLUSIONS: Other than a minor fall in HDL3 in women receiving transdermal 17beta-oestradiol, coadministration of oral progestogen in general improved, rather than worsened, this serum lipoprotein profile.