Pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration in surgical patients: simultaneous investigation of absorption and disposition kinetics using stable isotopes
The pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration were studied in 12 surgical patients using a stable isotope method. After subarachnoid administration of the agent to be evaluated, a deuterium-labelled analogue was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of the unlabelled and the deuterium-labelled local anesthetics were determined using a combination of capillary gas chromatography and mass fragmentography. Bi-exponential functions were fitted to the plasma concentration-time data of the deuterium-labelled local anesthetics. The progression of the absorption was evaluated using deconvolution. Mono- and bi-exponential functions were then fitted to the fraction absorbed versus time data. The distribution and elimination half-lives of the deuterium-labelled analogues were 25 +/- 13 min (mean +/- SD) and 121 +/- 31 min for lidocaine and 19 +/- 10 min and 131 +/- 33 min for bupivacaine. The volumes of the central compartment and steady-state volumes of distribution were: lidocaine 57 +/- 10 l and 105 +/- 25 l, bupivacaine 25 +/- 6 l and 63 +/- 22 l. Total plasma clearance values averaged 0.97 +/- 0.21 l/min for lidocaine and 0.56 +/- 0.14 l/min for bupivacaine. The absorption of lidocaine could be described by a single first order absorption process, characterized by a half-life of 71 +/- 17 min in five out of six patients. The absorption of bupivacaine could be described adequately assuming two parallel first order absorption processes in all six patients. The half-lives, characterizing the fast and slow absorption processes of bupivacaine, were 50 +/- 27 min and 408 +/- 275 min, respectively. The fractions of the dose, absorbed in the fast and slow processes, were 0.35 +/- 0.17 and 0.61 +/- 0.16, respectively.
- Research Organization:
- University Hospital, Leiden (Netherlands)
- OSTI ID:
- 6603051
- Journal Information:
- Anesthesiology; (United States), Vol. 69:4
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANESTHETICS
BIOCHEMICAL REACTION KINETICS
ABSORPTION
BIOLOGICAL HALF-LIFE
DEUTERIUM
GAS CHROMATOGRAPHY
PATIENTS
SURGERY
TISSUE DISTRIBUTION
TRACER TECHNIQUES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMATOGRAPHY
DISTRIBUTION
DRUGS
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MEDICINE
NUCLEI
ODD-ODD NUCLEI
REACTION KINETICS
SEPARATION PROCESSES
STABLE ISOTOPES
550201* - Biochemistry- Tracer Techniques
550600 - Medicine