Selective Androgen Receptor Modulator-Induced Liver Injury in Active Duty Male.

Selective androgenic receptor modulators (SARMs) are extensively advertised as safer and more effective analogues to traditional androgenic anabolic steroids, yet there are increasing cases of hepatotoxicity secondary to their use. We present the case of a previously healthy young active duty Marine who presented with cholestatic liver injury secondary to SARM use. This is the first reported case in a service member and contributes to the growing amount of evidence regarding the potential detrimental effects of SARMs. It also illustrates the impact of SARMs on military members and overall mission readiness as his treatment course included hospitalization and placement in a non-deployable status until recovery from his liver injury. Additional steps should be taken to increase awareness in order to protect service members and sustain readiness.

Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats.

Metoprolol is a selective ß1-adrenergic receptor antagonist metabolized by hepatic cytochrome P450s (CYPs). In this study, we evaluated pharmacokinetic changes following intravenous (i.v.) and oral metoprolol in rats with diabetes mellitus induced by streptozotocin (DMIS). Metoprolol has an intermediate hepatic extraction ratio in rats (0.586-0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism. Thus, the hepatic clearance, CL(H) (the non-renal clearance, CL(NR)) of metoprolol depends on the hepatic blood flow rate (Q(H)), the free fraction in plasma (f(p)), and in vitro hepatic intrinsic clearance, CL(int). After i.v. administration of 1.5 mg/kg metoprolol to DMIS rats, its CLNR was 40.9% faster than control animals. This could be due to a significantly faster QH because hepatic CL(int) and fp were comparable between the two groups of rats due to unchanged hepatic CYP2D activity. After oral administration of 1.5 mg/kg metoprolol to DMIS rats, gastrointestinal absorption was >99% of the oral dose for both groups, while the area under the curve (AUC) was 27.9% smaller, which could be caused by the greater hepatic metabolism seen in the i.v. study. These findings have potential therapeutic implications, assuming that the DMIS rats qualitatively reflect similar changes in patients with diabetes.

Does obesity affect the accuracy of prostate-specific antigen (PSA) for predicting prostate cancer among men undergoing prostate biopsy.

UNLABELLED: What's known on the subject? and what does the study add?: As most urologist known, obesity significantly lowers serum PSA levels. So there is some concern about delayed diagnosis of prostate cancer in obese men. In the present study, we found that the accuracy level of PSA for detecting prostate cancer was not significantly different between different obesity levels. A well-designed study adjusting for several factors, e.g. diet, exercise, medication and comorbidity, which may possibly compensate for the associated effects on PSA levels, is needed for confirmation of the present findings. OBJECTIVE: To investigate prostate-specific antigen (PSA) accuracy in detecting prostate cancer according to body mass index (BMI) in Asian men with a PSA level of <30 ng/mL using contemporary multicore (≥ 12) prostate biopsy. PATIENTS AND METHODS: We reviewed the records of 3471 patients, whose initial PSA levels were <30 ng/mL, who underwent multicore (≥ 12) transrectal ultrasound-guided prostate biopsy between January 2004 and May 2011. BMI was categorised as performed previously for the Asian population: <23, 23-24.9, 25-29.9, and ≥ 30 kg/m(2) . PSA accuracy for detecting prostate cancer in each BMI group was assessed based on the receiver operating characteristics-derived area under the curve. RESULTS: The mean age and median PSA level were inversely associated with BMI; the median PSA level in each BMI category was 7.84, 7.75, 7.33 and 5.79 ng/mL, respectively (P < 0.001). In all, prostate cancer was detected from biopsy in 1102 (31.7%) patients. The PSA accuracy for predicting prostate cancer in all patients was estimated to be 0.607, and PSA accuracies in each BMI category were 0.638, 0.572, 0.613 and 0.544, respectively; there was no significant difference among the groups in terms of PSA accuracy. CONCLUSIONS: The accuracy of PSA in predicting prostate cancer did not change regardless of BMI category in Asian men. However, as patients with higher BMIs had lower PSA levels than those with lower BMIs, it can therefore be suggested that the PSA threshold should be lower in obese men to discriminate between prostate cancer and benign conditions in the real clinical situation.

Pharmacokinetics of itraconazole in diabetic rats.

After intravenous or oral administration of 10 mg/kg itraconazole to rats with streptozotocin-induced diabetes mellitus and to control rats, the total area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24) for itraconazole and that for its metabolite, 7-hydroxyitraconazole, were similar between the two groups of rats. This may be explained by the comparable hepatic and intestinal intrinsic clearance rates for the disappearance of itraconazole and the formation of 7-hydroxyitraconazole in both groups of rats.