Dosing Variability and Clinical Outcomes of Oxybutynin: A Pediatric Cohort of Patients With Neurogenic Bladder.

Background: Despite the therapeutic advancements of the last several decades, neurogenic bladder remains a significant source of morbidity for patients with a spinal pathology. Oxybutynin is a mainstay of treatment in pediatric populations despite significant side effects and highly variable bioavailability. Objectives: To characterize the use of oxybutynin in a cohort of pediatric patients with neurogenic bladder. Methods: Retrospective data were collected of dosing, drug interactions, and urodynamics parameters in the 100 consecutive patients in a spinal differences clinic who had an appointment between October 7, 2015, and December 30, 2015. In addition to descriptive statistics, a linear regression model of oxybutynin dose versus age and sex was developed to examine the impact of age on dosing variability. Results: One hundred patients (52% female) with a median age of 6.8 years were included. The median daily dose of oxybutynin was 0.36 mg/kg (interquartile range, 0.28-0.54 mg/kg). Of the 48 patients with a recent urodynamics study, 13 had a detrusor leak point pressure (DLPP) greater than the typical cutoff of 40 cm H2O, indicating a need for management escalation. However, of these 13 patients, 38% were already on or exceeding oxybutynin's maximum recommended dose. Conclusion: The wide dosing variability and high DLPPs despite maximal dosing indicate a need for further investigation of oxybutynin's bioavailability in this population compared to its side effects and clinical outcomes. If variability in response to the medication is due to differences in bioavailability, then a precision-dosing model based on patient genomics could be developed for oxybutynin.

Characterization of perioperative androgen profiles in men with bladder cancer undergoing radical cystectomy.

BACKGROUND: Prior studies have demonstrated declines in androgen levels in men with cancer and patients undergoing anesthesia and surgery. In this study, we hypothesized that decreased serum androgen levels are prevalent in male patients undergoing radical cystectomy (RC) for bladder cancer and that it persists in the postoperative period. We characterized perioperative androgen hormonal profiles and examined for associated changes indicative of sarcopenia on computed tomography scans in men undergoing RC. METHODS: We implemented a prospective observational trial in men with newly diagnosed non-metastatic bladder cancer undergoing RC. Baseline pre-operative total testosterone (TT), free testosterone (FT), and luteinizing hormone (LH) were obtained on morning lab draws with 30 days of surgery. TT and FT were then repeated on postoperative days (POD) 2, 3, 30, and 90. The threshold for normal TT was defined as >300 ng/dl, consistent with the AUA Guidelines for Evaluation and Management of Testosterone Deficiency. We evaluated postoperative changes in weight and psoas muscle cross-sectional area using computed tomography scans to assess for sarcopenic changes. RESULTS: Univariable statistical analysis was performed. 25 patients were enrolled. The mean patient age was 68.9 years. The mean pre-operative TT was 308 ng/dl, and 12/23 (52.5%) patients had low testosterone. Mean TT onPOD 2 and 3 were 166 ng/dl and 161 ng/dl, respectively (range 24-345). 19/20 (95%) of men who had morning lab draws had decreased TT. The mean TT at 30 days was 253 ng/dl with 37.5% of men having low TT. Mean TT at 90 days was 306 ng/dl. The mean FT levels were 43 ng/dl, 29.25 ng/dl, 28.2 ng/dl, 40.89 ng/dl, and 42.62 ng/dl at baseline, POD 2, POD 3, POD 30, and POD 90, respectively. Mean LH at baseline was 9.9 IU/L. Average weight loss at 30- and 90- days postop was -4.29 and -4.38 kilograms, respectively. Weight loss was persistent with only 3/23 (13%) returning to their presurgery weight by 90 days. Despite significant declines in weight and perioperative TT, no significant differences in psoas muscle cross-sectional area were observed (net change -92 mm2, P= 0.13) CONCLUSIONS: Perioperative disruption of androgen levels is prevalent in men undergoing RC. Our trial demonstrates a pre-op, immediate postop, 30- and 90-day postoperative prevalence of low TT of 52%, 95%, 63%, and 37.5%, respectively. Significant changes in baseline weight were noted, although no significant changes in psoas muscle cross-sectional area were observed, limiting conclusions regarding a link between changes in androgens and sarcopenia in this setting.