Bioavailability of trospium chloride after intravesical instillation in patients with neurogenic lower urinary tract dysfunction: A pilot study

Abstract

Oral drug treatment of detrusor overactivity often causes undesirable side effects in other organs. For some patients, in particular those with neurogenically induced detrusor overactivity (detrusor hyperreflexia), the tolerance level for adverse effects is low and oral treatment may become ineffective. Intravesical administration of the drug can diminish the side effects or increase treatment effectivity in patients who are (partially) refractory to oral treatment because the relative concentration of the drug is increased in the target organ and decreased in the circulation. Six men (19–34 years old) with traumatic spinal cord lesions between C2 and Th11 were randomized to intravesical instillation with 15 or 30 mg trospium chloride in 40 ml saline into the empty bladder. Catheterization was postponed until at least 3 h after instillation, and fluid intake was not allowed during the first 4 h. Blood samples were taken before and 11 times after instillation; the last sample 12 h post instillation. Four positive samples were found in three patients: 0.10 ng/ml after 1 h and 0.13 ng/ml after 2½ h in two patients with 15 mg, and 0.24 ng/ml after 30 min and 0.70 ng/ml after 6 h in one patient with 30 mg instilled trospium chloride. Three adverse effects were reported and were rated as probably not related to the drug. It is concluded that intravesically instilled trospium chloride is not absorbed into the circulation in significant amounts and, thus, it may be expected that this mode of administration will improve the efficacy of trospium chloride therapy by reducing the side effects. Neurourol. Urodynam. 18:447–453, 1999. © 1999 Wiley‐Liss, Inc.

Comparison of Receptor Binding Characteristics of Commonly Used Muscarinic Antagonists in Human Bladder Detrusor and Mucosa

“…Furthermore, intravesical instillation of oxybutynin (De Wachter and Wyndaele, 2003), tolterodine (Yokoyama et al, 2005), and darifenacin (Iijima et al, 2007) reduces distension-evoked activity of C-fiber afferents in rat bladder, an effect also seen after systemic administration of oxybutynin (De Laet et al, 2006). In patients with overactive bladder, intravesical administration of muscarinic antagonists, such as oxybutynin and trospium, is associated with reduced adverse affects (Madersbacher and Jilg, 1991;Fröhlich et al, 1998;Walter et al, 1999), whereas clinical efficacy remains (Enzelsberger et al, 1995;Fröhlich et al, 1998). Intravesical instillation of muscarinic antagonists may be a useful approach in neurogenic patients because these patients are already undertaking clean intermittent self-catheterization.…”

“…Clinical trials with some of the newer antagonists have demonstrated a beneficial effect on urgency (Freeman et al, 2003;Chapple et al, 2004;Zinner et al, 2004;Millard and Halaska, 2006;Wagg et al, 2006); this symptom is not attributable to activation of muscarinic receptors on the detrusor. Furthermore, the efficacy of intravesically applied antimuscarinic agents strengthens the case for a role for muscarinic receptors associated with the bladder mucosa (Madersbacher and Jilg, 1991;Enzelsberger et al, 1995;Fröhlich et al, 1998;Walter et al, 1999).…”

Advances in intravesical therapy for urinary tract disorders

“…Depending on physicochemical characteristics of instilled drug, studies demonstrate that only 1–7% of instilled dose reaches the systemic circulation after instillation 87, 88 . Instilled drugs also avoid the first pass effect of orally administered drugs 89 .…”