Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC 0-ؕ ) showed an increase in amprenavir AUC 0-ؕ of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC 0-ؕ was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC 0-ؕ . The relationship between the total bilirubin concentration and the AUC 0-ؕ of amprenavir was well characterized by a simple E max model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of ␣ 1 -acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.
Immediate preoperative EUS may make it possible to select the best form of treatment in patients with CBD stones, avoiding inappropriate laparoscopic instrumental CBD exploration.
Case report of a young woman, aged 27, suffering from severe megaloblastic anemia due to folic acid deficiency. The factor responsible for this deficiency seems to be the regular use of oral contraceptives for 3 years (Noracycline 22®). Recent investigation evidenced the existence of selective malabsorption of food folates, due to the action of hormonal contraceptives on the intestinal conjugase. It can thus be admitted that contraceptive drugs play a prominent part in the genesis of this type of anemia. However, other factors must also be considered, like malnutrition and a masked malabsorption syndrome. The relation with megaloblastic anemia in pregnancy is discussed
134 patients with radiolucent gallstones were randomly allocated to receive either placebo or 1 of 3 different doses of chenodeoxycholic acid (CDCA); 750, 1,500, or 3,000 mg). The initial dose was lowered if not well tolerated. 107 patients were treated for more than 3 months. Among them, stones dissolved in 21 and were smaller in 25 patients. Partial or complete dissolution occurred in 4 of the 13 receiving 375 mg/day, 14 of 37 receiving 750 mg, 24 of the 38 receiving 1,500 mg and 4 of 8 receiving 3 000 mg/day. The number of responders to the therapy was significantly greater in the groups of patients receiving 1,500 mg/day or 17–24 mg/kg body weight than in any other group. However, side effects, i.e., diarrhea and transaminase increase, are also dose related. It appears from this study that the optimal dose of CDCA may be between 17 and 20 mg/kg body weight.
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