THE INFLUENCE OF ADRENALINE ON THE PHARMACOKINETICS OF INTERPLEURALLYADMINISTERED 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. F ive patients received an interpleural dose of lidocaine (200 mg; contr ol group), and 5 patients received an interpleural dose of lidocaine ( 200 mg) plus adrenalin (1:200,000). Plasma and cerebrospinal fluid (CS F) levels of lidocaine were measured before and at specified times (up to 8 hours) after the dose. The analytical technique was radioimmunoa ssay; and plasma and CSF data were assessed using noncompartmental ana lysis. The drug was quickly absorbed into the plasma in the control gr oup (C-max = 2.76 +/- 0.10 mu g/mL at 0.33 +/- 0.14 hours after admini stration); whereas drug access to CSF was decreased and occurred slowl y (C-max = 0.32 +/- 0.07 mu g/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 simult aneous administration of adrenalin delayed absorption (t(max) = 0.91 /- 0.52 hours). The drug elimination half-lives in plasma and CSF of t his group increased to 3.22 +/- 1.22 hours and 8.71 +/- 3.28 hours, re spectively. 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 adre nalin. From these results the levels that would be reached on a multip le-dose regimen (D = 200 mg, tau = 8 hours) were predicted, In the sec ond group, the drug accumulated in the CSF. This may lead to adverse c entral nervous system (CNS) side effects when adrenalin is given simul taneously with lidocaine.