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The pharmacokinetics of piritramide after prolonged administration to intensive care patients

Published online by Cambridge University Press:  23 December 2004

T. Bouillon ,
P. Groeger  and
D. Kietzmann
T. Bouillon
Affiliation:
Inselspital Berne, Department of Anaesthesia and Intensive Care Medicine, Berne, Switzerland; University of Goettingen, Goettingen, Germany
P. Groeger
Affiliation:
Department of Anaesthesia and Critical Care Medicine, Goettingen, Germany Present address: Department of Anaesthesia and Intensive Care Medicine, University of Halle-Wittenberg, Germany.
D. Kietzmann
Affiliation:
Department of Anaesthesia and Intensive Care Medicine, Goettingen, Germany Present address: Department of Anaesthesia and Intensive Care Medicine, University of Uppsala, Uppsala, Sweden.
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Abstract

Summary

Background and objective: The purpose of the present study was to determine the pharmacokinetics of the μ-agonist opioid pirinitramide (piritramide) after prolonged administration.

Methods: Nine patients requiring intensive care therapy and artificial ventilation for several days received piritramide with a median infusion rate of 5 mg h−1 (range 4.8–10 mg h−1) for a median period of 69.9 h (range 49–89 h) for analgesia and sedation. After the end of the infusion, frequent arterial blood samples were withdrawn for 96 h and assayed for piritramide using a gas chromatographic method. Standard compartmental models were fitted to the individual concentration–time courses to characterize the elimination of piritramide after prolonged administration.

Results: The concentration–time course after the end of the infusion was adequately described with a three-compartment model in eight patients and a two-compartment model in one patient (standard two-stage geometric mean and 16–84% quantile: volumes of distribution V1 = 47.9 (26.8–85.8) L, V2 = 402 (241–672) L, V3 = 332 (124–885) L; clearances Cl1 = 66.5 (53.2–83.0)L h−1, Cl2 = 215 (125–369)L h−1, Cl3 = 18.4 (9.2–36.8) L h−1). Both the steady-state volume of distribution (782 L) and the terminal elimination half-life (17.4 h) were larger than predicted from single bolus pharmacokinetic studies (412.5 L and 10.4 h, respectively), the context-sensitive half-time after more than 72 h of administration was 32% shorter than predicted (285 vs. 420 min).

Conclusions: Despite increasing terminal elimination half-life and volume of distribution at steady state (increasing drug load for a given plasma concentration), the context-sensitive half-time of piritramide after3 days of administration is lower than predicted from bolus kinetics, making the drug a suitable candidate for intensive care unit analgesia.

Keywords

ANALGESICS, OPIOID, piritramide pharmacokineticsINTENSIVE CARE, sedation, analgesiaDRUG ADMINISTRATION SCHEDULE, infusion, bolus
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 21 , Issue 9 , September 2004 , pp. 673 - 678
Copyright
2004 European Society of Anaesthesiology

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References

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