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Background: Cyclizine is used in the treatment and prevention of nausea and vomiting. We aimed to demonstrate bioequivalence between two formulations of cyclizine 50 mg tablets., Methods/results: This single-dose, two-treatment, two-period, two-sequence, open-label, randomized crossover study was conducted on 32 healthy male volunteers. The average values for Cmax, Tmax, AUC0-t and AUC0-inf were 21.50 ng/ml, 3.85 h, 423.71 ng.h/ml and 489.26 ng.h/ml, for cyclizine 50 mg (test) versus 20.39 ng/ml, 4.34 h, 410.56 ng.h/ml and 473.86 ng.h/ml for Valoid 50 mg (reference). The 90% CI of the mean ratios of Cmax (geometric mean ratio: 101.81 ng/ml), and AUC0-t (101.81 ng.h/ml) were within the bioequivalence range of 80 to 125%. Both drugs were well tolerated., Conclusion: Cyclizine 50 mg is bioequivalent to the reference.

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.)

A 70-year-old man was admitted to our hospital because of dyspnea after taking an antihistaminic agent (homochlorcyclizine hydrochloride) for itching. Chest roentgenogram showed infiltration in the left lung field, and laboratory data revealed eosinophilia. Examination of the bronchoalveolar lavage fluid revealed an increased eosinophil count. A drug lymphocyte stimulation test was positive only for calcium stearate, an additive contained in the homochlorcyclizine hydrochloride tablet. The pulmonary infiltration and clinical symptoms subsided after withdrawal of all drugs and initiation of glucocorticoid therapy. Therefore, we concluded that this patient's pulmonary disease was caused by calcium stearate, an additive for an antihistaminic drug. An allergic reaction to a drug's additive material should be considered as a rare cause of drug-induced acute eosinophilic pneumonia.

Forty-nine patients undergoing elective total hip replacement received either morphine or meptazinol for postoperative analgesia from a patient-controlled analgesia apparatus. Ventilatory rate and volume and arterial oxyhaemoglobin saturation were recorded continuously for the first 24 h following surgery. Episodic hypoxaemia was seen in both groups, associated with disturbances in ventilatory pattern. There was no significant difference in the incidence or severity of observed hypoxia between the groups, or with respect to the class of ventilatory disturbance. Mean linear analogue scores for pain and nausea were significantly (P less than 0.05) greater in the meptazinol group than in the morphine group 8 h after operation, but did not differ significantly at any other time. The mean number of demands for analgesic drugs was similar in the two groups. The meptazinol group had a greater requirement for anti-emetic drugs than the morphine group (P less than 0.05). It was concluded that meptazinol and morphine in equianalgesic doses had similar effects on ventilation in the postoperative period.

Self administered questionnaires completed by 69 out of 100 consecutive drug addicts attending two drug dependence clinics suggested that some private general practitioners were easily persuaded to prescribe controlled drugs. These drugs were usually methadone, dipipanone-cyclizine (Diconal), and methylphenidate (Ritalin). Numbers of new narcotic addicts notified to the Home Office confirmed the practice, which may lead to a severe spread of addiction, as occurred in the 1960s with heroin and cocaine. If the General Medical Council or a tribunal set up in accordance with the Misuse of Drugs Act 1971 cannot stop the practice, then the present licensing system should be extended to include all controlled drugs.