Estimating drug solubility in the gastrointestinal tract.

Solubilities measured in water are not always indicative of solubilities in the gastrointestinal tract. The use of aqueous solubility to predict oral drug absorption can therefore lead to very pronounced underestimates of the oral bioavailability, particularly for drugs which are poorly soluble and lipophilic. Mechanisms responsible for enhancing the luminal solubility of such drugs are discussed. Various methods for estimating intra-lumenal solubilities are presented, with emphasis on the two most widely implemented methods: determining solubility in fluids aspirated from the human gastrointestinal tract, and determining solubility in so-called biorelevant media, composed to simulate these fluids. The ability of the biorelevant media to predict solubility in human aspirates and to predict plasma profiles is illustrated with case examples.

Evaluation of serum prolactin levels in patients with endometriosis and infertility.

The aim of this study was to clarify the significance of serum prolactin concentrations in patients with infertility and endometriosis. Forty patients with infertility and laparoscopically proven endometriosis were recruited into the study. Basal serum prolactin levels and prolactin levels after TRH administration were measured. The mean basal serum prolactin concentrations were 12.5, 16.5, 19.5, and 26.5 ng/ml and those after thyrotropin-releasing hormone (TRH) administration were 88.3, 114.2, 125.3 and 138.8 ng/ml in patients with stages I, II, III and IV endometriosis, respectively. A statistically significant relationship was found between the basal serum prolactin levels as well as those after TRH injection and the stage of the endometriosis. The patients were divided in two groups. Group I consisted of 20 patients who did not receive any treatment, while group II consisted of 20 patients who were initially treated with GnRH analogues for 24 week and subsequently with several therapeutic schemes in order to improve their fecundity. The pregnancy rate was not different between the two groups. The patients, however, who did not become pregnant had higher serum prolactin concentrations after TRH administration as compared to those who conceived. We conclude that occult hyperprolactinemia may be a cause of infertility in patients with endometriosis.

Lipid intolerance does not account for susceptibility to alcoholic and gallstone pancreatitis.

BACKGROUND/AIMS: Hypertriglyceridemia is an established cause of pancreatitis and has been suggested as a predisposing factor in alcohol and gallstone-induced pancreatitis. The aims of this study were to determine fasting and postprandial triglyceride levels of alcoholics with pancreatitis, alcoholics without pancreatitis, patients with previous gallstone pancreatitis, patients with choledocholithiasis, and healthy controls. METHODS: Oral lipid tolerance studies were performed in the above groups. RESULTS: No relationship was found between alcoholic pancreatitis and hypertriglyceridemia, regardless of whether subjects were studied in the fasting state, after ingestion of fat, or after ingestion of fat with ethanol. Plasma triglyceride levels of alcoholics with pancreatitis remained similar to those of alcoholics without pancreatitis, but levels in both groups varied in relation to recent alcohol intake. Plasma triglyceride levels from both groups of alcoholics were greater than those of nonalcoholic healthy subjects. In addition, the previously reported association between postprandial hypertriglyceridemia and gallstone pancreatitis was not observed. CONCLUSIONS: Plasma triglyceride levels do not account for individual susceptibility to either alcoholic or gallstone pancreatitis.