The Influence of Adrenalin on the Pharmacokinetics of Interpleurally Administered Lidocaine in Patients With Pancreatic Neoplasia

The influence of adrenalin on the pharmacokinetics of lidocaine given interpleurally to 10 patients with pancreatic neoplasia was studied. Five patients received an interpleural dose of lidocaine (200 mg; control group), and 5 patients received an interpleural dose of lidocaine (200 mg) plus adrenalin (1:200,000). Plasma and cerebrospinal fluid (CSF) levels of lidocaine were measured before and at specified times (up to 8 hours) after the dose. The analytical technique was radioimmunoassay; and plasma and CSF data were assessed using noncompartmental analysis. The drug was quickly absorbed into the plasma in the control group (Cmax = 2.76 ± 0.10 μg/mL at 0.33 ± 0.14 hours after administration); whereas drug access to CSF was decreased and occurred slowly (Cmax = 0.32 ± 0.07 μg/mL at 1.66 ± 1.35 hours). The drug was eliminated more quickly from plasma than from CSF, with half‐lives of 1.71 ± 0.43 hours and 3.86 ± 1.27 hours, respectively. The simultaneous administration of adrenalin delayed absorption (tmax = 0.91 ± 0.52 hours). The drug elimination half‐lives in plasma and CSF of this group increased to 3.22 ± 1.22 hours and 8.71 ± 3.28 hours, respectively. The duration of the analgesia, evaluated as the time until the patient needed another dose, increased from 8.2 ± 1.5 hours in the control group to 9.7 ± 1.3 hours in the group that received adrenalin. From these results the levels that would be reached on a multiple‐dose regimen (D = 200 mg, r = 8 hours) were predicted. In the second group, the drug accumulated in the CSF. This may lead to adverse central nervous system (CNS) side effects when adrenalin is given simultaneously with lidocaine.