The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats

T. Okutomi, Y. Matsumoto, M. Saito, M. Shimizu, S. Hoka, K. M. Kuczkowski

Research output: Contribution to journalArticle

Abstract

Background: Bupivacaine is the agent most often used for labor analgesia. However, the risk of accidental intravascular injection of this drug and consequent acute systemic toxicity is ever-present. Although hydroxyethylstarch (HES) is preferred over crystalloid for prevention of hypotension during regional anesthesia, the pharmacokinetics of bupivacaine during fluid preloading has not been studied. Methods: Twenty-four awake Sprague-Dawley rats were randomly allocated to receive the continuous intravenous infusion of HES 70K, 200K or 400K, or normal saline (NS). After 1 hour of prehydration all animals received bupivacaine, 1mg kg-1, bolus, followed by a continuous infusion, 0.4mg kg-1 min-1 for 15 minutes. After the completion of bupivacaine infusion serial arterial blood samples to determine the plasma bupivacaine concentration were obtained. The plasma concentration-time profile of bupivacaine was fitted to a two-compartment open model, and the estimated intercepts and slopes were used for calculation of standard pharmacokinetic parameters. Results: The mean peak bupivacaine concentration during HES 400K infusion was significantly lower than during NS infusion (1488 ±302 ng ml-1 vs 2388 ± 582 ng ml -1). Mean volume of distribution in each of the three HES groups was greater than in NS group. Mean area under curves (AUC) during HES 200K and HES 400K infusions were significantly lower than during NS infusion (32534 ± 4180 and 29619 ± 4431 min ng ml-1, respectively, vs 39802 ± 6268 min ng ml-1). Mean total clearance of bupivacaine during HES 200K and HES 400K infusions was significantly higher than during NS infusion (115 ± 14 and 132 ± 15 ml min-1kg -1, respectively, vs 92 ± 14 ml min-1 kg -1). Conclusion: Our results suggest that the increased volume of distribution during HES infusion could be counterbalanced by the increased total clearance, resulting in unchanged half-life or elimination rate constant of bupivacaine.

Original languageEnglish
Pages (from-to)259-264
Number of pages6
JournalActa Anaesthesiologica Belgica
Volume57
Issue number3
Publication statusPublished - Sep 2006
Externally publishedYes

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Bupivacaine
Pharmacokinetics
Conduction Anesthesia
Intravenous Infusions
Hypotension
Analgesia
Area Under Curve
Sprague Dawley Rats
Half-Life
Injections

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Okutomi, T., Matsumoto, Y., Saito, M., Shimizu, M., Hoka, S., & Kuczkowski, K. M. (2006). The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats. Acta Anaesthesiologica Belgica, 57(3), 259-264.

The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats. / Okutomi, T.; Matsumoto, Y.; Saito, M.; Shimizu, M.; Hoka, S.; Kuczkowski, K. M.

In: Acta Anaesthesiologica Belgica, Vol. 57, No. 3, 09.2006, p. 259-264.

Research output: Contribution to journalArticle

Okutomi, T, Matsumoto, Y, Saito, M, Shimizu, M, Hoka, S & Kuczkowski, KM 2006, 'The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats', Acta Anaesthesiologica Belgica, vol. 57, no. 3, pp. 259-264.
Okutomi T, Matsumoto Y, Saito M, Shimizu M, Hoka S, Kuczkowski KM. The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats. Acta Anaesthesiologica Belgica. 2006 Sep;57(3):259-264.
Okutomi, T. ; Matsumoto, Y. ; Saito, M. ; Shimizu, M. ; Hoka, S. ; Kuczkowski, K. M. / The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats. In: Acta Anaesthesiologica Belgica. 2006 ; Vol. 57, No. 3. pp. 259-264.
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AU - Kuczkowski, K. M.

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