Setsuko Murase

Neurotoxicity of intrathecally administered bupivacaine involves the posterior roots/posterior white matter and is milder than lidocaine in rats

Background and Objectives Clinical and laboratory studies suggest that lidocaine is more neurotoxic than bupivacaine. However, histological evidence of their comparative neurotoxicity is sparse. We thus pathologically and functionally compared the intrathecal neurotoxicity of these agents. Methods Rats received 0.12 μL/g body weight lidocaine (0%, 2%, 10%, or 20%) or bupivacaine (0%, 0.5%, 2.5%, or 5%) in distilled water via an intrathecal catheter. The influence of high osmolarity was also examined using 5% bupivacaine in 20% glucose solution (5% BG) and a control 25% glucose solution. The L3 spinal cord, the posterior and anterior roots, and the cauda equina were examined by light and electron microscopy. Walking behavior and sensory threshold were investigated as neurofunctional tests. Results The posterior root and posterior white matter showed axonal degeneration in rats treated with 10% and 20% lidocaine and 5% bupivacaine in distilled water (5% BDW) and in 5% BG, but not in rats treated with 2% lidocaine, 0.5% and 2.5% bupivacaine, distilled water, or 25% glucose solution. The histological damages were more severe in 20% lidocaine-treated rats than in 5% bupivacaine-treated rats. The damage of posterior white matter was observed only when the posterior root was severely injured. No significant difference of histological findings was observed between 5% BDW and 5% BG. Functional abnormalities were found only in rats treated with 20% lidocaine. Conclusions The neurotoxic lesions caused by bupivacaine and lidocaine were indistinguishable in the primary site and the extending pattern, such as axonal degeneration originating from the posterior roots and extending to the posterior white matter. The intrathecal neurotoxicity is greater in lidocaine than in bupivacaine.

Determination of Serum Mexiletine Concentrations and its Protein Binding by High-performance Liquid Chromatography.

A new method to determine serum mexiletine (MX) concentrations using high-performance liquid chromatography (HPLC) was established.This method could reduce a sample volume to 100μ1 of serum and could shorten the pretreatment time to less than 10 minutes by using Chem Elut minicolumn. The results obtained by this method (n=28) correlated well with those obtained by gas chromatography method (r=0.997).Moreover, this method had a good recovery and reproducibility, suggesting that it is an excellent method for determining serum MX concentrations.Using this HPLC method, serum protein binding of MX was studied in healthy subjects and patients with chronic renal failure (CRF). The protein binding of MX was 60.83±4.37% in healthy subjects (n=6) and 52.45±6.22% in CRF (n=9).The protein binding of MX in CRF was significantly decreased, compared with healthy subjects, indicating an apparent elevation of free drug concentrations.In general, dose adjustment of MX in CRF is considered to be unnecessary. However, free drug concentrations may participate in the appearance of effects and adverse reactions. The possibility of enhanced pharmacological effects and increased adverse reactions due to such variations of protein binding in CRF should be also considered.

Stability of Aminoglycoside Antibiotics in Anemopathy

Stability of aminoglycosides (AG) in anemopathy was investigated in regard to change in appearance and in pH, smell and residual potency by compatibility tests using Alevaire, and influence of ultrasonic nebulization. In this study, commercially available injections of gentamicin (GC), kanamycin (KC), streptomycin (SC), amikacin (BK), dibekacin (PM) and tobramycin (TC) were used. The results are summarized as follows:1) No changes in appearance and pH were observed in all the solutions of AG mixed with Alevaire. BK and PM kept primary potency for 168 hours after mixing, but the potency of GC began to decrease 24 hours after, and also that of KC, SC and TC decreased slightly 6 to 168 hours after. 2) AG was stable even under the influence of ultrasonic nebulization, though a bad smell was given out from additives in AG injections due to their decomposition.From these results, it is emphasized that: 1) AG should be mixed just before use, and 2) attention should be paid to odor and taste, as well as residual potency.

Study on Compatibility of Urokinase with Other Drugs

Compatibility tests on Urokinase (UK) with 39 kinds of drugs prescribed in combination with UK in our hospital were performed in terms of visible change, pH and residual potency of UK as determined by fibrin-plate method after the mixture. The results may be summarized as follows:determined by fibrin-plate method after the mixture. The results may be summarized as follows:1) Mixture of UK and Calcicol or Persantin showed precipitation immediately after mixing, while mixture of UK and Keflin, K. C. L., Penbritin or Celtol showed a decrease in potency 0-3 hours after mixing. Therefore, these mixtures are incompatible.2) Mixture of UK and Solita T3, Pydoxal, Vitamedin, Vitaneurin, MDS or Novoheparin showed a decrease in potency 6 hours after mixing. Hence these mixtures should be made carefully.

Compatibility of Commercial Gentamicin Injection with Six Drugs for Inhalation

Compatibility of commercial gentamicin injection (GC) with six drugs for inhalation (Alevaire, Bisolvon, Asthone, Asthpul, Alotec and Venetlin) was investigated on 15 models of mixture in terms of change in appearance, pH and residual potency in microbioassay. It was found that in all these models the potency of GC deteriorated 0-3 days after mixture.