BackgroundEthanol is included in certain injectable preparations of anticancer drugs to increase their solubility. Since the volume of ethanol in these preparations is approximately half of the total injection volume, the potential inhibitory effects of ethanol on the central nervous system cannot be disregarded, especially considering that patients may drive immediately after administration of the medication. Therefore, the concentration of ethanol was examined in exhaled breath after administration of paclitaxel, an anticancer medication containing ethanol.MethodsThe ethanol concentration in exhaled breath immediately after an intravenous infusion of paclitaxel was measured in 30 patients, using a balloon-type gas detector tube. Correlations between the concentration of ethanol in exhaled breath and the total amount of ethanol administered or the intravenous infusion speed were calculated.ResultsThe mean ethanol concentration in exhaled breath was 0.028 ± 0.015 mg/L. The correlation between the ethanol concentration in exhaled breath and the total dose of ethanol was weak (R2 = 0.25; p = 0.055), while the intravenous infusion speed showed a stronger positive correlation with the concentration of ethanol in the breath (R2 = 0.49; p = 0.11). The maximum concentration of ethanol measured in exhaled breath (0.06 mg/L) was equivalent to 40% of the threshold for drunk driving, as specified in the Road Traffic Act in Japan.ConclusionIn this study, no patient had a breath ethanol concentration exceeding the legal threshold for drunk driving. However, it is still advisable for patients to avoid driving after receiving paclitaxel injections. When driving cannot be avoided, patients should wait for a sufficient time after receiving the injection before driving.

In order to treat a hyperammonemic patient with adult-onset type-II citrullinemia (CTLN2), sodium phenylacetate powder was prepared from chemical reagent grade phenylacetic acid in Gunma University Hospital. After purification by recrystalization, phenylacetic acid was neutralized with sodium carbonate and dried at 70°C under reduced pressure. A solution of the prepared powder produced a single peak of m/z‫0.181؍‬ (M؉Na ؉ ) in electrospray-ionization-MS spectrogram. The content of phenylacetate was 74% of theoretical value, suggesting the existence of water of crystallization. The content of phenylacetate remained constant for 5 months under dark conditions at room temperature. The prepared sodium phenylacetate powder was orally administered to a 16-year-old patient with CTLN2 at a dosage of 12 g/d. The serum ammonia concentration of the patient, who did not show adequate response to intravenous arginine or oral sodium benzoic acid decreased remarkably to less than 100 m mg/dl. Sodium phenylacetate powder should be an essential drug for the treatment of hyperammonemia caused by an inborn error of the urea cycle.Key words phenylacetate; hyperammonemia; pharmacy In the human body, the urea cycle is the major pathway for the disposal of waste nitrogen, and inborn errors of this pathway, including type-II citrullinemia (CTLN2) which shows a liver-specific decrease of argininosuccinate synthetase, may reduce the nitrogen flux. As a result, there is an accumulation of ammonia and disordered metabolism of other amino acids. Episodic hyperammonemia is observed in these patients, often resulting in coma and death. Serum ammonia can be reduced by administration of sodium benzoate and phenylacetate, since these compounds can produce the respective amino acid acylation products, hippurate or phenylacetylglutamine, resulting in an increase in urinary nitrogen.1) Although the efficacy of phenylacetate for the treatment of hyperammonemia has been well established, 2-7) the use of phenylacetate or benzoic acid for the treatment of hyperammonemia is not approved in Japan. Benzoic acid is sometimes prescribed as an unlabeled use drug, while phenylacetate was rarely used because of legal controls. Additionally, as phenylacetic acid has an unpleasant smell, it must be changed to sodium salt for clinical use, because sodium phenylacetate is not commercially available in Japan. We report the case of a hyperammonemic patient who was successfully treated with sodium phenylacetate powder, which was prepared at the manufacturing section of the Department of Pharmacy in Gunma University Hospital. Clinical details of the patient have been reported elsewhere. 8)All reagents except for phenylacetic acid were purchased from commercial sources and were used without further purification. Chemical reagent grade phenylacetic acid was purchased from Wako Pure Chemical Industries (Osaka, Japan). Since the reagent appeared to be light-yellow color, the phenylacetic acid was recrystallized to remove impurities. Fifty grams of phenylacetic acid were d...

Background: Ethanol is included in certain injectable preparations of anticancer drugs to increase their solubility. Since the volume of ethanol in these preparations is approximately half of the total injection volume, the potential inhibitory effects of ethanol on the central nervous system cannot be disregarded, especially considering that patients may drive immediately after administration of the medication. Therefore, the concentration of ethanol was examined in exhaled breath after administration of paclitaxel, an anticancer medication containing ethanol. Methods: The ethanol concentration in exhaled breath immediately after an intravenous infusion of paclitaxel was measured in 30 patients, using a balloon-type gas detector tube. Correlations between the concentration of ethanol in exhaled breath and the total amount of ethanol administered or the intravenous infusion speed were calculated. Results: The mean ethanol concentration in exhaled breath was 0.028 -0.015 mg/L. The correlation between the ethanol concentration in exhaled breath and the total dose of ethanol was weak (R 2 = 0.25; p = 0.055), while the intravenous infusion speed showed a stronger positive correlation with the concentration of ethanol in the breath (R 2 = 0.49; p = 0.11). The maximum concentration of ethanol measured in exhaled breath (0.06 mg/L) was equivalent to 40% of the threshold for drunk driving, as specified in the Road Traffic Act in Japan. Conclusion: In this study, no patient had a breath ethanol concentration exceeding the legal threshold for drunk driving. However, it is still advisable for patients to avoid driving after receiving paclitaxel injections. When driving cannot be avoided, patients should wait for a sufficient time after receiving the injection before driving.

In Japan, the initial dose of 2.5 mg/3 d is recommended in the package insert of the fentanyl patch preparation to substitute for oral morphine in the dose range of 45 135 mg/d (90 mg/d at the midpoint), while a higher dose is recommended in other countries. To validate the recommended dose of this drug in Japan, we investigated how long the initial recommended dose of the fentanyl patch could control the pain of cancer patients after the switch from other opioids. The dose of the fentanyl patch was increased on the 20th day after the switch from prior opioids at a lower dose than the midpoint of the indicated range, while it was increased on the 3rd day after the switch from the higher dose of prior opioids. Regression analysis showed that the e‹cacy ratio of the fentanyl patch : oral morphine＝80 : 1, suggesting that oral morphine of 25 75 mg/d should be substituted for by the fentanyl patch preparation at a dose of 2.5 mg/3 d.

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