ABSTRACT
The frequency distribution of CYP3A activity was investigated by measuring ratios of urinary 6beta-hydroxycortisol to free cortisol in 487 healthy subjects to determine whether a genetic polymorphism for this cytochrome enzyme exists in "native-born" Japanese persons. Spot urine samples (from 9:00 am to 12:00 pm) were collected for measurement of 6beta-hydroxycortisol and free cortisol by high-performance liquid chromatography with a CN column after extracting with a solid-phase column (Bond-Elut C18). The frequency distribution of the urinary 6beta-hydroxycortisol to free cortisol was widely distributed among subjects but with no clear bimodality by a probit plot. Furthermore, the frequency distribution assessed on a new normal test variable plot indicated the possible existence of a CYP3A sexual dimorphism. Mean 6beta-hydroxycortisol levels were higher in women (n = 249) than in men (n = 238) by 1.7-fold, and this difference was statistically significant (P < 0.01). These results show that a CYP3A genetic polymorphism in Japanese persons, based on 6beta-hydroxycortisol excretions, likely does not exist, but there appears to be a broad unimodal distribution of enzyme activity in the population.
Subject(s)
Hydrocortisone/analogs & derivatives , Hydrocortisone/urine , Adolescent , Adult , Chromatography, High Pressure Liquid , Creatinine/urine , Female , Humans , Japan , Male , Reference Values , Regression Analysis , Sex CharacteristicsABSTRACT
OBJECTIVES: The purpose of this study was to develop, implement, and assess estimation procedures to prevent adverse drug reactions (ADRs), especially drug-induced metabolic disorders, based on the subjective symptoms (complaints) of patients. METHODS: Our own database called CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information System) was started in 1987 and now contains ca. 23,000 case reports of ADRs. We extracted 264 cases of drug-induced metabolic disorders from CARPIS, such as hyperglycemia, hypoglycemia, and hypokalemia. Evaluation scores were created based on the subjective symptoms and the backgrounds of these patients. The scores were applied to the 264 cases to demonstrate their efficiency in estimation of ADRs. RESULTS: The evaluation scores estimated ADRs as follows: 39.6% of the 96 hyperglycemia cases, 53.6% of the 84 hypoglycemia cases, and 59.5% of the 84 hypokalemia cases. The validity measures of the evaluation scores were estimated to be as follows: for hyperglycemia sensitivity (SE) = 39.6%, specificity (SP) = 99.0%, predictive value of positive test (PVP) = 97.4%, positive likelihood ratio (PLR) = 39.6, and negative likelihood ratio (NLR) = 0.61; for hypoglycemia, SE = 53.6%, SP = 93.0%, PVP = 86.5%, PLR = 7.7 and NLR = 0.50; and for hypokalemia, SE = 59.5%, SP = 99.0%, PVP = 98.0%, PLR = 59.5, and NLR = 0.41. CONCLUSIONS: The proposed evaluation scores are a reliable estimation method to detect ADRs related to drug-induced metabolic disorders. The scores should be incorporated into the integrated ADR estimation system available at a Web site our institution is developing, along with other evaluation scores of drug-induced liver disorders, extrapyramidal symptoms, and leakopenia, and druy eruptions.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hyperglycemia/chemically induced , Hypoglycemia/chemically induced , Hypokalemia/chemically induced , Patient Participation , Adverse Drug Reaction Reporting Systems , Databases, Factual , Humans , Hyperglycemia/diagnosis , Hyperglycemia/epidemiology , Hypoglycemia/diagnosis , Hypoglycemia/epidemiology , Hypokalemia/diagnosis , Hypokalemia/epidemiologyABSTRACT
Morphine is used to alleviate chronic cancer pain. However, constipation is a major adverse effect that often detracts from the patient's quality of life. In this study, we investigated the effectiveness of dietary fiber on morphine-induced constipation. Rats were fed on a normal diet or one containing either 10% or 20% apple fiber for two weeks before morphine was administered. In the control diet group, the fecal number and dry weight were decreased by treating with morphine in a dose-dependent manner. Moreover, the motility of the small and large intestines was reduced. The fecal number and weight were increased and the colon motility was promoted by dietary fiber, regardless of whether morphine was being administered. The dietary fiber increased the concentration of short-chain fatty acids (SCFAs) in the cecum. These results suggest that dietary fiber has a preventative effect on morphine-induced constipation by increasing SCFAs in the cecum, and thereby promoting colon motility in rats.
