The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients: a stable-isotope study

Simon, M. J. G.; Veering, Bernadette; Stienstra, Rudolf; Kleef, Jack W. van; Williams, Steven G.; McGUIRE, G. M.; Burm, A. G. L.

doi:10.1097/00003643-200406000-00008

Cited by 19 publications

(37 citation statements)

References 27 publications

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“…This study confirmed that, like other amide local anesthetics, the systemic absorption of ropivacaine after epidural administration occurs by two absorption processes, i.e., an initial rapid phase followed by a slower phase (4,6,14,16,19). In addition, the F 1 was larger in the youngest compared with the two oldest age groups, although the difference between the youngest and oldest patients was not significant.…”

Section: Discussionsupporting

confidence: 81%

“…Studies performed in our institution under quite similar conditions (4,6,16,19) showed nearly equal F 1 values for bupivacaine and ropivacaine. The F 1 of levobupivacaine seems to be somewhat less, which may be explained by the greater vasoconstrictive action of this drug (16,20). Vasoconstriction of the epidural vessels may decrease the uptake of local anesthetics from the epidural space into the systemic circulation.…”

Section: Discussionmentioning

confidence: 71%

“…However, it is possible that this process is counteracted by a decreased local distribution, which is accounted for by the lower lipid solubility of ropivacaine. The t ½,a1 of ropivacaine was longer than those found for the other long-acting local anesthetics bupivacaine and levobupivacaine (4,6,16). The vasoconstrictive action of ropivacaine may delay the initial absorption of the local anesthetic.…”

Section: Discussionmentioning

confidence: 86%

“…Arterial blood samples were collected up to 24 h after epidural administration with intervals gradually increasing from 5 min to 4 h (16). Samples were stored on ice and centrifuged for 10 min at 1500g and 4°C within 4 h. The plasma was transferred into prelabeled tubes and stored at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

“…Details of the pharmacokinetic analysis have been described earlier (6,16). Disposition kinetics were derived by fitting bi-exponential and tri-exponential functions to the plasma concentration-time data of D3-ropivacaine, using weighted (1/predicted concentration squared) least-squares nonlinear regression analysis with the software package WinNonlin version 4.1 (Pharsight Corp, Mountain View, CA).…”

Section: Methodsmentioning

confidence: 99%

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The Effect of Age on the Systemic Absorption and Systemic Disposition of Ropivacaine after Epidural Administration

Simon

Veering²,

Vletter³

et al. 2006

Anesthesia &Amp; Analgesia

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Knowledge about the systemic absorption and disposition of ropivacaine after epidural administration is important in regard to its clinical profile and the risk of systemic toxicity. We investigated the influence of age on the pharmacokinetics of ropivacaine 1.0% after epidural administration, using a stable-isotope method. Twenty-four patients were enrolled in 1 of 3 groups according to age (group 1: 18-40 yr; group 2: 41-60 yr; group 3: > or =61 yr). Patients received 150 mg ropivacaine hydrochloride epidurally. After 25 min, patients received 50 mL 0.44 mg/mL deuterium-labeled ropivacaine (D3-ropivacaine) IV. Arterial blood samples were collected up to 24 h after epidural administration. Total plasma concentrations of ropivacaine and D3-ropivacaine were determined using liquid chromatography mass spectrometry. In the oldest patients, elimination half-life was significantly longer (ratio of the geometric means 0.60; 95% confidence interval, 0.37-0.99) and clearance was significantly decreased (mean difference, 194 mL/min; 95% confidence interval, 18-370 mL/min) compared with the youngest patients. The systemic absorption was biphasic. Absorption kinetics for ropivacaine (fractions absorbed: (F1, F2) and half-lives: (t(1/2),a1), t(1/2),a2) during the fast and slow absorption process: 0.27 +/- 0.08 and 0.77 +/- 0.12, respectively; 10.7 +/- 5.2 min and 248 +/- 64 min, respectively) were in the same range as for other long-acting local anesthetics. F1 was on average 0.11 (95% confidence interval, 0.002-0.22) higher in the youngest compared with the middle age group. Observed age-dependent pharmacokinetic differences do not likely influence the risk of systemic toxicity in the elderly after a single epidural dose of ropivacaine.

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Section: Discussionsupporting

confidence: 81%