OBJECTIVE: To investigate the influence of oral contraceptives on cytochrome P450 3A4 (P450NF) activity. METHODS: In 23 healthy women, the pharmacokinetics of nifedipine and its main metabolite dehydronifedipine in plasma were assessed after a single oral dose, prior to and after intake of one of two oral contraceptive formulations, one containing 2 mg dienogest and 0.03 mg ethinylestradiol (group A) and the other containing 0.125 mg levonorgestrel and 0.03 mg ethinylestradiol (group B). RESULTS: While the intake of two oral contraceptives for 21 days did not influence the plasma concentration-time curve of unchanged nifedipine, mean AUC0-23.5 h and the mean Cmax values of dehydronifedipine were significantly lower in both groups tested/(24% in group A and 25% in group B). This observation may indicate a reduced formation rate of metabolites and reflects an inhibition of cytochrome P450 3A4 activity. The activation of the same or other metabolic degradation mechanism(s) could explain this result. CONCLUSION: The investigation presented demonstrates the importance of metabolite measurement when in vivo studies are undertaken to investigate different influences on drug metabolizing ability.

Adult↗

PubMedDate not supplied

Assessment of breast tissue changes on hormonal replacement therapy using MRI: a pilot study.

PURPOSE: The purpose of this study was to investigate, using MRI, the potential morphologic effects of hormonal replacement therapy (HRT) on breast tissue in post-menopausal women. METHOD: Five subjects were enrolled who were treated subsequently with both estrogen (2 mg/day) and a combination of estrogen (2 mg/day) and progestagen (1 mg/day). T1-weighted (TR 11 ms, TE 4.65 ms, flip angle 35 degrees, two excitations) 3D MR scans were acquired on a 1.5 T whole-body scanner before therapy and after each regimen. With use of a segmentation algorithm and histogram evaluation, parenchymal tissue/fat ratios were calculated over targeted volumes and changes were assessed. RESULTS: An increase in these ratios was observed in two subjects after receiving the combined therapy, indicating a change in parenchymal pattern, whereas no obvious changes were detected in any of the subjects during the estrogen-based therapy. CONCLUSION: MRI is able to detect and quantitate changes in breast parenchyma during HRT.

Adult↗