摘要:

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were stuudied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320–400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35–55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 ± 0.46 (mean ± SD) μg/ml following the first injection and 3.34 ± 0.76 μg/ml after the second, to 4.11 ± 0.72 μg/ml following the third. The maximum concentrations of MEGX and GX were 0.66 ± 0.22 and 0.28 ± 0.08 μg/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2= 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 ± 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 ± 0.61 1/kg), and clearance divided by bioavailability (Cl/F, 11.65 ± 1.21 ml·kg−1·min−1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (±6 μg/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing. By considering the relative potencies of MEGX and GX to the parent drug and their concentrations attained, it is felt that MEGX, but not GX, may play an additive role in causing possible toxicity following epidural lidocaine. The authors recommend that the plasma concentration of lidocaine be monitored when the mean cumulative epidural dose of lidocaine HCl exceeds 900 mg.

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

A bioassay, using high-performance liquid chromatography (HPLC) analysis of platelet adenosine nucleotides and hypoxan-thine, was studied for its potential use as a test for MH susceptibility. A protocol for the assay was developed, based on the method outlined by Solomons and Masson. The HPLC procedure was a rapid, efficient, sensitive, and highly reproducible technique for measuring ATP, ADP, AMP, and hypoxanthine in platelets. Conditions of extraction and storage were critical for preventing degradation of the nucleotides. Extraction of nucleotides at ice-bath temperature was found necessary. Storage of platelet extract in PCA, even at −20° C, showed loss of ATP and ADP; hence, neutralization with KOH was essential before storage. Contrary to the findings of Solomonset al., the present study demonstrated that neither ATP depletion nor per cent reduction in nucleotide ratios in platelets treated with halothane can be used as a definitive test for the diagnosis of MH susceptibility. The reason for this disagreement is unclear; however, differences in methods and altitude are implicated. It is possible that the platelet is not affected by malignant hyperthermia and thus cannot serve as a test system for the detection of the syndrome.

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1985

数据来源: OVID