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Titolo:
Concentration-effect relationship of cisatracurium at three different doselevels in the anesthetized patient
Autore:
Bergeron, L; Bevan, DR; Berrill, A; Kahwaji, R; Varin, F;
Indirizzi:
Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada Univ Montreal Montreal PQ Canada H3C 3J7 rm, Montreal, PQ H3C 3J7, Canada Univ British Columbia, Vancouver Gen Hosp, Dept Anesthesia, Vancouver, BC V5Z 1M9, Canada Univ British Columbia Vancouver BC Canada V5Z 1M9 ver, BC V5Z 1M9, Canada
Titolo Testata:
ANESTHESIOLOGY
fascicolo: 2, volume: 95, anno: 2001,
pagine: 314 - 323
SICI:
0003-3022(200108)95:2<314:CROCAT>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
OPIOID BARBITURATE ANESTHESIA; ATRACURIUM BESYLATE; TWITCH DEPRESSION; ADDUCTOR POLLICIS; SURGICAL PATIENTS; MUSCLE-RELAXANTS; PHARMACOKINETICS; PHARMACODYNAMICS; ELIMINATION; PLASMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Varin, F Univ Montreal, Fac Pharm, CP 6128,Succursale Ctr Ville, Montreal,PQ H3C 3J7, Canada Univ Montreal CP 6128,Succursale Ctr Ville Montreal PQ Canada H3C 3J7
Citazione:
L. Bergeron et al., "Concentration-effect relationship of cisatracurium at three different doselevels in the anesthetized patient", ANESTHESIOL, 95(2), 2001, pp. 314-323

Abstract

Background The linearity of cisatracurium elimination and its concentration-effect relation were determined as part of a traditional rich data study with three dose levels in patients receiving balanced anesthesia. Methods. Forty-eight adults with American Society of Anesthesiologists status T-H were randomized to receive an intravenous bolus dose of 0.075, 0.15, or 0.30 mg/kg cisatracurium. Anesthesia was induced and maintained with nitrous oxide-oxygen, propofol, and fentanyl. The mechanical response of theadductor pollicis muscle was recorded. Arterial blood samples were collected over 8 h. Cisatracurium, laudanosine, and the monoquaternary alcohol concentrations were measured by high-performance liquid chromatography. To assess the relative contribution of the input function, a parametric (assumingelimination from both the central and peripheral compartments) and a nonparametric pharmacokinetic-pharmacodynamic model were both applied to data. Results. Dose proportionality of the body disposition of cisatracurium. and its two major metabolites at doses up to 0.30 mg/kg was confirmed. With the parametric approach, the effect compartment concentration at 50% block (EC50) Significantly increased with the dose (136 vs. 157 vs. 209 ng/ml), whereas the effect compartment equilibration rate constant decreased (0.0675 vs. 0.0568 vs. 0.0478 min(-1)). A similar dose-dependent effect of the pharmacokinetic-pharmacodynamic relation was observed with the nonparametric approach, but the trend was 50% less pronounced. Conclusion: A dose-related change in pharmacokinetic-pharmacodynamic parameters was identified with both modeling approaches. A pharmacokinetic origin was ruled out, although no definite explanation of the underlying mechanism could be provided. These findings suggest that doses relevant to the anesthetic practice be used for estimation of EC50.

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Documento generato il 31/03/20 alle ore 15:16:29