American journal of clinical and experimental urology · 2023
Does large volume of distribution of lidocaine masks its systemic uptake from bladder?
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Tyagi Pradeep, Ganguly Anirban, Chermansky Christopher, Tarin Tatum V, Yoshimura Naoki, Maranchie Jodi
Аннотация
PURPOSE: To assess whether therapeutic and toxic effects of intravesical lidocaine are determined by coincident serum levels.
MATERIAL AND METHODS: Published clinical trials and case studies on instilled lidocaine 1-2% that reported serum lidocaine levels were analyzed using model independent pharmacokinetic equations to compute the absorbed dose fraction (F) for linear regression with the respective dwell times.
RESULTS: Rapid absorption of intravesical lidocaine is evinced by the serum levels of 0.16±0.3 mg/L at 5 min in bladder cancer patients coinciding with the rapid onset of pain relief (<5 min) and blood pressure drop (≥10 mm Hg) in spinal cord injured patients. Serum levels at 5 min are raised five-fold by alkalinization for a tertiary amine with pKa of 7.8 and a linear rise in F with longer dwell time (r2 = 0.80; P<0.005) conforms to passive, paracellular diffusion of amphiphilic lidocaine (log P of 1.68) around umbrella cell borders with absorption rate at least five times faster than the terminal elimination rate, and therefore the delay in blood sampling after instillation is unwarranted. A rapid resolution of therapeutic and toxic effects is predicated on the extensive dilution of absorbed lidocaine with a rapid distribution half-life of 3.6 min in body weight dependent Vd - 15 times larger than blood volume, 0.13-4.5 L/kg which necessitates dose adjustment in children.
CONCLUSION: Whether rapid absorption of instilled lidocaine is complicated by an equally rapid and extensive dilution in body weight dependent Vd can be resolved by early blood sampling (<30 min) for: evidence-based medicine, avoidance of lidocaine toxicity in children and to educate the evolution of lidocaine solution to gel and devices.
MATERIAL AND METHODS: Published clinical trials and case studies on instilled lidocaine 1-2% that reported serum lidocaine levels were analyzed using model independent pharmacokinetic equations to compute the absorbed dose fraction (F) for linear regression with the respective dwell times.
RESULTS: Rapid absorption of intravesical lidocaine is evinced by the serum levels of 0.16±0.3 mg/L at 5 min in bladder cancer patients coinciding with the rapid onset of pain relief (<5 min) and blood pressure drop (≥10 mm Hg) in spinal cord injured patients. Serum levels at 5 min are raised five-fold by alkalinization for a tertiary amine with pKa of 7.8 and a linear rise in F with longer dwell time (r2 = 0.80; P<0.005) conforms to passive, paracellular diffusion of amphiphilic lidocaine (log P of 1.68) around umbrella cell borders with absorption rate at least five times faster than the terminal elimination rate, and therefore the delay in blood sampling after instillation is unwarranted. A rapid resolution of therapeutic and toxic effects is predicated on the extensive dilution of absorbed lidocaine with a rapid distribution half-life of 3.6 min in body weight dependent Vd - 15 times larger than blood volume, 0.13-4.5 L/kg which necessitates dose adjustment in children.
CONCLUSION: Whether rapid absorption of instilled lidocaine is complicated by an equally rapid and extensive dilution in body weight dependent Vd can be resolved by early blood sampling (<30 min) for: evidence-based medicine, avoidance of lidocaine toxicity in children and to educate the evolution of lidocaine solution to gel and devices.