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- W4249308957 abstract "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 After the end of the infusion, frequent arterial blood samples were withdrawn for 96 h and assayed for piritramide using a gas chromatographic method.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 (782L) 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 after 3 days of administration is lower than predicted from bolus kinetics, making the drug a suitable candidate for intensive care unit analgesia." @default.
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- W4249308957 date "2004-09-01" @default.
- W4249308957 modified "2023-09-26" @default.
- W4249308957 title "The pharmacokinetics of piritramide after prolonged administration to intensive care patients" @default.
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- W4249308957 doi "https://doi.org/10.1097/00003643-200409000-00001" @default.
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