Pain intensity and bioavailability of intramuscular asparaginase and a local anesthetic: a double-blinded study.
ABSTRACT To evaluate if dissolution of asparaginase in lidocaine can relieve pain of an intramuscular injection in children without changes in bioavailability.
The study was designed as a double-blinded study, randomizing 12 children with acute lymphoblastic leukemia (ALL) to four different combinations of injections, including two injections where asparaginase was dissolved in a lidocaine solution and two in sterile water. Seventeen treatment courses of asparaginase, each consisting of four injections, were evaluated. Pain intensity (Pain Visual Analog Scale, VAS-score) and pharmacokinetics of the drug was evaluated.
The pain scores showed a significant difference between the two solutions of asparaginase (+/-lidocaine) (P value < 0.0001). Lidocaine did not influence the pharmacokinetics of the drug.
Asparaginase with addition of lidocaine significantly decreases the pain as measured by the visual analog scale without changing the bioavailability or the absorption rate of the enzyme.
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ABSTRACT: The visual analog scale (VAS) is a tool widely used to measure pain, yet controversy surrounds whether the VAS score is ratio or ordinal data. We studied 52 postoperative patients and measured their pain intensity using the VAS. We then asked them to consider different amounts of pain (conceptually twice as much and then half as much) and asked them to repeat their VAS rating after each consideration (VAS2 and VAS3, respectively). Patients with unrelieved pain had their pain treated with IV fentanyl and were then asked to rate their pain intensity when they considered they had half as much pain. We compared the baseline VAS (VAS1) with VAS2 and VAS3. The mean (95% confidence interval) for VAS2:1 was 2.12 (1.81-2.43) and VAS3:1 was 0.45 (0.38-0.52). We conclude that the VAS is linear for mild-to-moderate pain, and the VAS score can be treated as ratio data. IMPLICATIONS: A change in the visual analog scale score represents a relative change in the magnitude of pain sensation. Use of the VAS in comparative analgesic trials can now meaningfully quantify differences in potency and efficacy.Anesthesia & Analgesia 01/2000; 89(6):1517-20. · 3.30 Impact Factor
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ABSTRACT: L-Asparaginase has been widely used for the treatment of acute lymphoblastic leukemia. Therapeutic and toxic effects in the central nervous system have been noted with systemic treatment. In order to better define the relationship between L-asparaginase administration and cerebrospinal fluid (CSF) asparagine levels, L-asparaginase and asparagine were measured in the CSF of rhesus monkeys following intrathecal and i.v. administration. Following intrathecal injection, the enzyme activity of Escherichia coli L-asparaginase in the CSF demonstrated a more rapid terminal half-life than did that of 111In-labeled diethylenetriaminepentaacetic acid, a marker of CSF bulk flow [4 +/- 0.7 (S.D.) hr versus 5.8 +/- 0.2 hr]. Intrathecal injection of E. coli asparaginase resulted in complete depletion of CSF asparagine for at least 5 days. A similar period of CSF asparagine depletion was observed following i.v. administration of L-asparaginase. Similar results were found in seven patients undergoing systemic L-asparaginase therapy. The minimal plasma level of L-asparaginase necessary to deplete CSF asparagine in both species was 0.1 IU/ml. Two other enzymes, Erwinia L-asparaginase and succinylated Acinetobacter glutaminase-asparaginase, were cleared from the CSF at the same rate as bulk flow. These data indicate that systemic L-asparaginase therapy may be a feasible means of treating central nervous system involvement in patients with acute lymphoblastic leukemia and that there is no therapeutic advantage to using intrathecal L-asparaginase.Cancer Research 12/1981; 41(11 Pt 1):4554-8. · 8.65 Impact Factor
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ABSTRACT: To describe the pharmacokinetics of Erwinia asparaginase (ASNase) after intravenous (i.v.) and intramuscular (i.m.) administration. A group of 29 children with newly diagnosed acute lymphoblastic leukemia (ALL) received Erwinia ASNase 30,000 IU/m2 every day for 10 days during multiagent induction therapy. Of these patients. 13 received i.v. therapy and 16 received i.m. therapy. During the reinduction phase the patients received Erwinia ASNase 30,000 IU/m2 twice a week for 2 weeks (Mondays and Thursdays) (8 patients in the i.v.-treated group and 11 patients in the i.m.-treated group). ASNase activity (spectrophotometric assay) was measured in plasma samples obtained from the patients at various times during therapy. The estimated half-life was 6.4 +/- 0.5 h (n = 13), the absorption rate after i.m. administration was found to limit elimination. The apparent volume of distribution corresponded well with the volume of plasma. The estimated clearance suggested that Erwinia ASNase is a low-clearance drug. Bioavailability after i.m. administration was (mean +/- SEM) 27.0 +/- 4.5% (range 11-61%; n = 12). In this study the pharmacokinetic parameters after i.v. and i.m. administration of Erwinia ASNase were determined based on a substantial number of patients. The present findings emphasize the importance of conducting proper pharmacokinetic studies before a new drug or a new preparation of a drug is introduced in a different schedule.Cancer Chemotherapy and Pharmacology 08/2001; 48(1):77-82. · 2.80 Impact Factor