Steady-State Pharmacokinetics of Interpleural Bupivacaine in Patients after Cholecystectomy

Abstract

Venous plasma concentrations ofbupivacaine were determined in eight cholecystectomy patients following multiple interpleural bolus instillations of bupivacaine 20 ml O.S% with adrenaline (S mgll) administered at six-to eight-hour intervals. The mean steady-state peak plasma concentration was 2.3 mgll (range 1.2-3.1 mgll); however, in three of the eight patients peak plasma concentrations were greater than 3 mgll. The mean accumulation ratio was found to be 1.6 (range 0.99-2.49), with steady-state occurring within the first 24 hours of drug administration. Mean apparent systemic plasma clearance was 0.16±0. 07l!kglh with a mean terminal half-life of S.8±2.3 hours measured at steady-state, values which were not significantly different (P> O.OS) from those values obtained following single inter pleural bolus dose administration.

The disposition of bupivacaine following a 72 h interpleural infusion in cholecystectomy patients.

“…There remains a discrepancy between our data and that of Seltzer and colleagues (1987), who reported a shorter half-life and higher values of clearance and steady-state volume of distribution following single bolus interpleural injections of bupivacaine in cholecystectomy patients. Previously, we had attributed this discrepancy to a difference in technique and suggested that prolonged absorption of bupivacaine from the pleural cavity may have contributed to the kinetic differences found in our studies (Kastrissios et al, 1990;Mogg et al, 1990). However, since the present results from continuous infusion confirmed those from our previous bolus dose studies, this now appears less likely and our results may reflect a decrease in the elimination of the drug in patients with biliary disease.…”

“…The interpleural infusion regimen was determined empirically from pharmacokinetic data derived in our previous studies in order to produce a steady-state venous plasma concentration of 2 mg 1-1 (Kastrissios et al, 1990;Mogg et al, 1990). This concentration was chosen since it was representative of the mean steadystate drug concentration (2.3 ± 0.7 mg l-1) previously measured (Kastrissios et al, 1990) after intermittent interpleural administration of 20 ml doses of 0.5% bupivacaine HCl with adrenaline, the most commonly employed clinical dosage regimen.…”

“…All blood samples were centrifuged and the plasma fraction was collected and deep-frozen prior to analysis. Bupivacaine concentrations (as the base) were measured by high performance liquid chromatography (Wiegand & Chou, 1984), as described previously (Kastrissios et al, 1990). The sensitivity of the assay was 0.1 mg -l1, with an intraand inter-day assay coefficient of variation of approximately 8% at a plasma drug concentration of 0.4 mg -[.…”

“…There are little published pharmacokinetic data on interpleural bupivacaine (Kastrissios et al, 1990;Mogg et al, 1990;Seltzer et al, 1987). In previous studies, we have determined the pharmacokinetics of both single and multiple interpleural bolus doses of bupivacaine in post-cholecystectomy patients (Kastrissios et al, 1990;Mogg et al, 1990). As an extension of these studies, we sought to develop an effective interpleural infusion regimen for bupivacaine.…”

Interpleural analgesia for attenuation of postoperative pain after hepatic resection*

“…Numerous studies demonstrate an acceptable safety profile with bupivacaine administered via the interpleural route [6, 8, 12–14, 16, 19]. In our study we used a conservative dosing regime and found no reported symptoms consistent with local anaesthetic toxicity.…”