Search

Context: Cyclizine, an antihistaminic antiemetic, is commonly used in palliative care. Its pharmacokinetics have been poorly studied, and its metabolic pathway is unknown but may involve the genetically controlled cytochrome P450 2D6 (CYP2D6). If this is the case, the metabolic ratio of cyclizine to norcyclizine and efficacy/adverse effects may vary between patients according to their CYP2D6 genotype., Objectives: To deduce the pharmacokinetics and antiemetic/sedative effects of cyclizine and relate these and its metabolic ratio to the CYP2D6 genotype in palliative care patients., Methods: Palliative care patients initiated on continuous cyclizine subcutaneous (SC) infusions had blood samples taken and efficacy/toxicity scores measured during the approach to steady state. Another group of patients at steady state receiving oral cyclizine had a single blood sample taken. Samples were analyzed to elucidate pharmacokinetic parameters and CYP2D6 genetics., Results: SC dosing group: The median (interquartile range) cyclizine half-life, volume of distribution, and clearance were 13 (7-48) hours, 23 (12-30)L/kg, and 15 (11-26)mL/min/kg, respectively. Nausea and sedation scores were 3.0 (1.2-5.7) and 5.0 (2.6-8.1), respectively, overall and did not vary with genotype (P=0.76 and 0.11, respectively). The median overall metabolic ratio at steady state was 4.9 (3.8-9.2) and did vary with CYP2D6 genotype (P=0.02). Oral dosing group: The median metabolic ratio was 2.1 (1.5-2.9) and did not vary with CYP2D6 genotype (P=0.37)., Conclusion: Palliative care patients have similar cyclizine pharmacokinetics to those reported in other patient groups. Cyclizine metabolism to norcyclizine may include CYP2D6 as the metabolic ratio varied with CYP2D6 genotype in the SC group., (Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Background: Aminoglycoside-induced ototoxicity has been reported in neonates but its incidence is poorly defined, whereas vancomycin-induced ototoxicity has not been reported in neonates., Objective: To compare hearing test results in infants in a neonatal intensive care unit (NICU) who were or were not treated with extended interval gentamicin dosing and/or standard vancomycin dosing., Method: A database of otoacoustic emissions (OAE), over a 5-year period of NICU admissions, was combined with databases of gentamicin and vancomycin dosing to compare patients treated or not treated with these antibiotics., Results: A total of 2,347 OAE results was available. OAE failure rates were: no gentamicin and no vancomycin (noGnoV), 7% (85/1,233); gentamicin but no vancomycin (GnoV), 4% (42/949); vancomycin but no gentamicin (VnoG), 22% (9/41) and gentamicin and vancomycin (GandV), 14% (17/124). Compared to noGnoV there was a decreased risk of OAE failure in GnoV (p = 0.022, OR 0.64, 95% CI 0.44-0.94) and an increased risk in VnoG (p = 0.003, OR 3.46, 95% CI 1.54-7.75) and GandV, (p = 0.006, OR 2.20, 95% CI 1.26-3.83)., Conclusions: Gentamicin, as used and evaluated in this audit, showed no evidence of an increased risk of ototoxicity; what was observed was a statistically significant decrease in OAE failure rate. Vancomycin, by contrast, was associated with ototoxicity., (Copyright © 2011 S. Karger AG, Basel.)