Plasma levels of citalopram in depressed patients with hepatitis C.

Hepatitis C affects an estimated 4 million Americans and 100 million people worldwide. Rates of depression are higher than that seen in the general population. Antidepressant therapy is often initiated at lower doses in patients with liver disease because of concerns about impaired metabolism and clearance. This study assessed plasma levels of citalopram in 15 subjects with hepatitis C and major depression during an 8-week trial. The mean citalopram dose at study completion was 26.67 mg/day. Mean plasma levels of citalopram, compared with levels previously reported, were lower than expected (at 10 mg/day [N = 1]: 21 ng/ml [N = 1]; at 20 mg/day [N = 8]: mean = 42.25 ng/ml, SD = 18.38; at 30 mg/day [N = 1]: 54 ng/ml; at 40 mg/day [N = 5]: mean = 76.2 ng/ml, SD = 35.86). There was a tendency for lower plasma levels to be found in those subjects receiving interferon, although a statistically significant difference was not observed. Citalopram was well tolerated. The results of this study suggest that patients with major depression and hepatitis C, but without evidence of severe liver disease, may be able to tolerate usual recommended doses of citalopram, thus avoiding the potential for undertreatment of the depression.

Naphthalene-induced respiratory tract toxicity: metabolic mechanisms of toxicity.

The lung, which is in intimate contact with the external environment, is exposed to a number of toxicants both by virtue of its large surface area and because it receives 100% of the cardiac output. Lung diseases are a major disease entity in the U.S. population ranking third in terms of morbidity and mortality. Despite the importance of these diseases, key issues remain to be resolved regarding the interactions of chemicals with lung tissue and the factors that are critical determinants of chemical-induced lung injury. The importance of cytochrome P450 monooxygenase dependent metabolism in chemical-induced lung injury in animal models was established over 25 years ago with the furan, 4-ipomeanol. Since then, the significance of biotransformation and the reasons for the high degree of pulmonary selectivity for a myriad of different chemicals has been well documented, mainly in rodent models. However, with many of these chemicals there are substantial differences in the susceptibility of rats vs. mice. Even within the same species, varied levels of the respiratory tract respond differently. Thus, key pieces of data are still missing when evaluating the applicability of data generated in rodents to primates, and as a result of this, there are substantial uncertainties within the regulatory community with regards to assessing the risks to humans for exposure to some of these chemicals. For example, all of the available data suggest that the levels of cytochrome P450 monooxygenases in rodent lungs are 10-100 times greater than those measured in the lungs of nonhuman primates or in man. At first glance, this suggests that a significant margin of safety exists when evaluating the applicability of rodent studies in the human, but the issues are more complex. The intent of this review is to outline some of the work conducted on the site and species selective toxicity and metabolism of the volatile lung toxic aromatic hydrocarbon, naphthalene. We argue that a complete understanding of the cellular and biochemical mechanisms by which this and other lung toxic compounds generate their effects in rodent models with subsequent measurement of these cellular and biochemical events in primate and human tissues in vitro will provide a far better basis for judging whether the results of studies done in rodent models are applicable to humans.

An open-label trial of citalopram for major depression in patients with hepatitis C.

BACKGROUND: Hepatitis C affects nearly 4 million Americans. Depression is a common comorbid condition in this population and may be induced by interferon alfa, an approved treatment for hepatitis C. Depression is a major indicator for discontinuation of interferon therapy. This open-label study examines the effect of citalopram on measures of depression and quality of life and tests of liver function in subjects with hepatitis C and major depressive disorder. METHOD: Subjects were recruited by advertisement; those with DSM-IV major depressive disorder were included in the study. Subjects received citalopram for 8 weeks starting at 20 mg/day. Dosage adjustments were made as the physicians deemed clinically necessary. No dosages were increased prior to week 4 of the study. Hamilton Rating Scale for Depression (HAM-D) scores, Clinical Global Impressions-Severity of Illness scale (CGI-S) scores, Medical Outcomes Study Short Form Health Survey (SF-36) ratings, Symptom Checklist-90-Revised (SCL-90-R) scores, and liver function tests were obtained at baseline, 4 weeks, and 8 weeks. RESULTS: A total of 15 patients (10 men, 5 women) participated in this study. The mean daily dose of citalopram at endpoint was 26.67 mg. Mean HAM-D scores decreased significantly with treatment (F = 36.3, df = 2,42; p = .0001). Thirteen of the 15 subjects demonstrated a clinical response, defined as a 50% or greater reduction in HAM-D scores. CGI-Severity of Illness scores also improved significantly (p = .0001). Subjects demonstrated statistically significant improvement (p < .05) on all of the SF-36 subscales. Statistically significant improvements (p < .05) were also demonstrated on all subscales of the SCL-90-R. Tests of liver function showed no significant worsening of aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyltransferase levels. CONCLUSION: These results suggest that depression in patients with hepatitis C may be effectively and safely treated with citalopram.

Use of biomarkers in an indoor air study: lack of correlation between aromatic VOCs with respective urinary biomarkers.

The benzene and toluene levels inside of eight homes with attached garages were measured during July 1998 in Fairbanks, Alaska. A thermal desorption tube method and charcoal tube method were used to collect and analyze samples (thermal desorption tube method %RDS = 1.9 for n = 6; charcoal tube method %RDS = 6.5 for n = 4). Results for both methods were compared and showed indoor benzene levels ranging between 1.2 and 72 ppbv. The charcoal tube method usually gave lower results than the thermal desorption method. Nevertheless, the difference observed in benzene levels from each method was not significant as determined by application of the Wilcoxon t-test to these data. Using the thermal desorption method, the range of toluene found in homes was 0.1-111 ppbv. A correlation between toluene and benzene levels suggested the same point source. The benzene and toluene content of the indoor air and the number of small engines stored in the attached garage was also correlated. There was no correlation found between the urinary biomarker concentrations and the level of benzene or toluene measured inside the homes in the summer.