In an acute model of IC/BPS, rats were administered a single dose of intraperitoneal CYP 150mg/kg. Four hours after CYP administration, intravesical IMB-150 (34mM), or intravesical free lidocaine (34mM) was administered. Tactile sensitivity was measured at baseline, 6, 8 and 24 hr after CYP administration. In a chronic model of IC/BPS, rats received intraperitoneal 40 mg/kg CYP on days 0, 3 and 6. On day 7, animals received intravesical IMB-150 (11mM), or intravesical free lidocaine (11mM). Tactile sensitivity was assessed at baseline, 4hr after the last CYP dose and at 2, 4, 24, 48 and 72hr post-treatment. In both acute and chronic models of IC/BPS, tactile sensitivity was assessed using von Frey fibers of increasing force 1, 2, 4, 6, 8, 10, 15 and 26g at 5 second interstimulus intervals. The nociceptive threshold was defined as the force (g) for which the stimulus produced a nocifensive response. An integrated (area under the curve) analgesic effect was calculated using trapezoidal approximation for individual animals as the nociceptive threshold vs time graph from 6–24hr and 2–48hr for the acute IC/BPS and chronic IC/BPS models, respectively. A comparison of the integrated analgesic effect values of vehicle, free lidocaine, and IMB-150 was performed using an ordinary one-way analysis of variance (ANOVA) with a Tukey multiple comparisons test to assess differences between the groups.
To study safety and pharmacokinetics, adult beagle dogs were anesthetized, catheterized and given intravesical IMB-150 at low (2.4mg/kg), mid (7.2mg/kg) and high – maximally feasible dose (24mg/kg). All animals were administered IMB-150 once weekly for 8 weeks (a total of 8 administrations). Intravesical doses were held in the bladder for 1hr post-administration and subsequently the bladder was evacuated. Plasma lidocaine concentrations were measured on days 1, 22, and 50 corresponding to the first, fourth and last dose respectively. Urinary lidocaine concentrations were measured daily for 15 days after the last dose on week 8. Throughout the study and for a 2-week recovery period, assessments included mortality checks, clinical observations, body weight, food consumption, ophthalmology and electrocardiograms.