J Clin Pharmacol
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Articles

The influence of adrenalin on the pharmacokinetics of interpleurally administered lidocaine in patients with pancreatic neoplasia

B Calvo, JL Pedraz, AR Gascon, RM Hernandez, E Garcia-Ortega, F Vara, C Muriel, and A Dominguez-Gil

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 microgram/mL at 0.33 +/- 0.14 hours after administration); whereas drug access to CSF was decreased and occurred slowly (Cmax = 0.32 +/- 0.07 microgram/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, tau = 8 hours) were predicted.(ABSTRACT TRUNCATED AT 250 WORDS)
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