Association between tetracycline or doxycycline and hepatotoxicity: a population based case-control study.

BACKGROUND AND OBJECTIVE: An FDA Working Group, along with representatives of PhRMA and the American Association for the Study of Liver Diseases, as well as the Institute of Medicine Report 'To Err is Human: Building a Safer Health Care System' have suggested that post-marketing drug surveillance is a important method to decrease adverse drug events. While tetracyclines are known to cause hepatotoxicity, no post-marketing drug surveillance studies have examined the risk of developing hepatotoxicity with tetracyclines. Therefore, the objective of this study is to determine the difference in risk of hepatotoxicity in patients receiving doxycycline or tetracycline using California Medicaid claims. METHODS: This study used a retrospective, matched case-control study using California Medicaid claims data. The cases were defined as recipients who had at least one diagnosis of hepatotoxicity any time from 1 July 1999 to 31 December 2001. One control was identified for each case, matched on age, gender and race. Logistic regression was used to determine the adjusted odds ratio (OR) and 95% confidence intervals for current users and past users of tetracycline and doxycycline. Covariates controlled for in the analysis were age, use of other hepatotoxic drugs, renal dysfunction, pregnancy, and alcohol or illicit drug use. RESULTS: A total of 3377 cases of hepatotoxicity were identified. Current users and past users of tetracycline had a statistically significant increased risk of developing hepatotoxicity (current use OR 3.70, 95% CI 1.19-11.45; past use OR 2.72, 95% CI 1.26-5.85). Current users or past users of doxycycline did not have an increased risk of developing hepatotoxicity (current use OR 1.49, 95% CI 0.61-3.62; past use OR 1.74, 95% CI 0.99-3.06). Tetracycline was commonly used for acne, acute bronchitis and upper respiratory infections. Doxycycline was commonly used for acute bronchitis, vaginitis and acne. DISCUSSION AND CONCLUSION: Doxycycline was potentially less hepatotoxic than tetracycline. Doxycycline could potentially be a safe substitute for tetracycline, when appropriate.

Diagnostic testing.

The results of cardiac tests must always be interpreted through the lens of pretest probabilities created by the history and the physical examination. Tests should be chosen with a clear diagnostic and prognostic purpose in mind. A clear understanding of the relationship between the history and physical examination and more technologic diagnostic testing improves the primary care physician's ability to evaluate potential cardiac disease in an efficient and cost-effective manner.

4,4'-methylene-bis-ortho-chloro-aniline (MBOCA): absorption and excretion after skin application and gavage.

4,4'-methylene-bis-ortho-chloro-aniline ( MBOCA ) is an aromatic amine and industrial chemical that has been shown to cause cancer of several different organs in rats and mice and bladder cancer in dogs. The purpose of this study was to determine the efficacy of using urinary concentrations of MBOCA as a means for evaluating extent of exposure. Male Sprague-Dawley rats were given MBOCA and [14C] MBOCA by either gavage or skin application. Concentrations and amounts of 14C were measured in urine, feces, skin and total carcasses, and parent MBOCA in urine at several intervals after application. The percentages of administered doses excreted and retained in the animals were calculated and comparisons made. Within 72 hr after gavage 16.5% of the administered compound was excreted in urine as 14C but only 0.25% as parent MBOCA . In the same interval after skin application a maximum of 2.54% of administered MBOCA was excreted as 14C but only 0.008% as parent MBOCA . Seventy-two hours after gavage 13.7% of the administered dose was retained in the tissues, and after skin absorption 5-13% was retained. With gavage the rate of excretion of 14C in urine and feces was very high in the first 24 hr (68.3%) but fell off rapidly (2.07%) by the third day. After skin absorption the rates of excretion of 14C were fairly constant over a 3-day period. Less MBOCA was absorbed from the skin if the skin was washed within 8 hr after application, as compared to waiting 24 hr or not washing at all. The amount of parent MBOCA detected in urine is a very small amount of that applied or absorbed. The percentage detected and the rates of excretion depend upon the route of administration, and the interval between exposure and sampling. For these reasons urinary analysis for MBOCA can be used only as very imprecise indicators of extent of recent exposure.