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PubMed1980

[Improved antiemetic treatment with levomepromazine (author's transl)].

The antiemetic effect of levomepromazine (Neurocil) was tested in 76 patients treated for metastasizing malignancies with cis-dichlorodiammineplatinum (II) (Platinex). In all patients conventional antiemetics had been ineffective against gastrointestinal side effects of platinum. Using levomepromazine vomiting and nausea could be successfully prevented in 47 out of 63 patients on conventional cis-platinum doses (20 mg/m2 for 5 consecutive days) and in 5 out of 13 patients on high single day dosages (100 mg/m2). In most other patients clear-cut subjective improvement occurred. The antiemetic effect of levomepromazine against cis-platinum, which ranks among the most widely used cytostatics and causes gastrointestinal symptoms, is of importance in medico-oncological practice as it causes relief for the patients.

Cisplatin↗
PubMed1999

A previously unidentified acepromazine metabolite in humans: implications for the measurement of acepromazine in blood.

High-performance liquid chromatography-diode-array detection results obtained during the investigation of two cases involving acepromazine prompted us to study the stability of the drug in blood. It was found that acepromazine can undergo in vitro conversion by human red blood cells to 2-(1-hydroxyethyl)promazine, a product that has been reported as a minor urinary metabolite in horse urine but not previously identified in humans. Further, our analytical findings in the two cases examined suggest that 2-(1-hydroxyethyl)promazine may be the major unconjugated metabolite of acepromazine in humans. These findings have important implications for the analytical toxicology of acepromazine.

Acepromazine↗
PubMed1990

Fly larvae and their relevance in forensic toxicology.

Toxicological analyses on a putrefied cadaver are sometimes difficult to perform because of the absence of blood and urine. In this study, fly larvae, being living material, are proposed as a new medium of investigation in forensic toxicology. Bromazepam and levomepromazine were identified and assayed in the remains of cerebral tissue, in the clavicle of a putrefied cadaver, and in the fly larvae found on and in the corpse.

Aged↗
PubMed2000

Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine.

The cytochrome enzyme P450 2D6 (CYP2D6) is thought to play a role in the human metabolism of fluvoxamine. Levomepromazine is a potent inhibitor of CYP2D6. We coadministered a low dosage of levomepromazine and fluvoxamine in 15 patients and found that the low dosage of levomepromazine was effective in counteracting the fluvoxamine-induced insomnia and did not increase plasma fluvoxamine levels. These results suggest that the inhibition of CYP2D6 by levomepromazine has little effect on fluvoxamine metabolism. Therefore, a low dosage of levomepromazine, used as a hypnotic agent, appears to be effective and safe when coadministered with fluvoxamine. Since this was a pilot study without a placebo control, a double-blind placebo-controlled study is needed to confirm our preliminary findings.

Adult↗
PubMed1982

Active metabolites of neuroleptic drugs: possible contribution to therapeutic and toxic effects.

Recent studies demonstrating a relationship between plasma levels and effects of haloperidol, thioridazine, chlorpromazine, butaperazine, fluphenazine, and perphenazine suggest that therapeutic plasma level monitoring of neuroleptics may be clinically useful. Chlorpromazine, thioridazine, levomepromazine, and loxapine have active metabolites which attain plasma levels within the same range as that of the parent compound after therapeutic doses of the drug. The metabolites often have pharmacological profiles which are different from that of the parent drug, and some metabolites apparently contribute to the side effects of the drug but do not possess any neuroleptic potency. The ratios between the plasma levels of metabolites and the parent compound show large interpatient variations, and the metabolites should, therefore, be measured together with the parent drug by therapeutic plasma level monitoring. Accordingly, the assay method should be carefully selected in order to include metabolites which may contribute to the therapeutic or side effects of the drug.

Antipsychotic Agents↗
PubMed1997

Increased plasma concentrations of bromperidol and its reduced metabolite with levomepromazine, but not with thioridazine.

Bromperidol is a close structural analog of haloperidol. The authors studied the effects of levomepromazine and thioridazine, which are frequently added to other neuroleptics as sedatives, on plasma concentrations of bromperidol and its reduced metabolite. The subjects were 26 inpatients with schizophrenia receiving bromperidol, 12 to 24 mg/day, for 1 to 19 weeks. In 10 cases, 50 mg levomepromazine per day and in nine cases, 50 mg thioridazine per day were coadministered for 1 week. In seven cases, both drugs were coadministered with > or = 2-week intervals. Plasma concentrations of bromperidol and reduced bromperidol were measured by a high-performance liquid chromatographic method. Levomepromazine (n = 17) significantly (p < 0.001) increased plasma concentrations of bromperidol (7.3 +/- 4.1 versus 10.2 +/- 4.8 ng/ml) and reduced bromperidol (1.8 +/- 1.4 versus 4.5 +/- 3.3 ng/ml). Thioridazine (n = 16) did not significantly change plasma concentrations of bromperidol (9.1 +/- 5.7 versus 8.6 +/- 5.5 ng/ml), while those of reduced bromperidol could not be measured because of interfering peaks. The current study suggests that levomepromazine, but not thioridazine, increases plasma concentrations of bromperidol and reduced bromperidol by inhibiting the metabolism of these compounds.

Adult↗
PubMed2000

Solid-phase microextraction for the assay of levomepromazine in human plasma.

Solid-phase microextraction (SPME) was investigated as sample preparation for the assay of the neuroleptic drug levomepromazine in human plasma. A mixture of human plasma, water, chloramitriptyline as internal standard, and aqueous NaOH was extracted with a 100-microm polydimethylsiloxane (PDMS) fiber (Supelco). The desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C [HP 5890; BPX-5 (SGE): 30 m x 0.53 mm ID, 1-microm film capillary; nitrogen-phosphorus selective detection]. As repeatedly found for SPME analysis of drugs in plasma, the recovery was low (i.e., 7% for levomepromazine). However, the analyte and internal standard were well separated and the calibration was linear from 5 to 180 ng/mL. The within-day precision was 2%, 4%, and 19% at concentrations of 160 ng/mL, 80 ng/mL, and 5 ng/mL, respectively. The between-day precision was 3%, 7%, and 19%, respectively. The limit of determination was 5 ng/mL. The comparison with an established liquid-liquid extraction gas-liquid chromatography method revealed good agreement for spiked samples and patient samples. No interfering peaks of drugs coadministered with levomepromazine or of endogenous substances were found. It is concluded that the method can be used in the therapeutic drug monitoring and clinical toxicology of levomepromazine.

Antipsychotic Agents↗
PubMed2004

Intentional overdose of Large Animal Immobilon.

We describe a case of voluntary self-injection with Large Animal Immobilon, a veterinary anaesthesia product containing etorphine, a very strong opioid, and acepromazine, a phenothiazine. This resulted in cardiorespiratory arrest and the need for sustained haemodynamic support after resuscitation. Large Animal Immobilon is used under specific conditions only, mainly in zoo and wildlife medicine. Primary toxicological analysis, although guided by the presumed toxin, could only detect a metabolite of acepromazine in the urine. Further analysis was able to show some traces of etorphine. A number of topics are treated, including the apparent potency of the etorphine and the selection of a suitable antidote, taking into account the different properties of the respective agents.

APACHE↗
PubMed1979

Analgesic treatment with levomepromazine in acute myocardial infarction. A randomized clinical trial.

The efficacy of a non-narcotic analgesic is evaluated in a double-blind randomized series of patients with acute myocardial infarction (AMI). Levomepromazine or pethidine were given in 328 consecutive cases to 316 patients within 24 hours after the onset of symptoms. Levomepromazine, 12.5 mg, appeared as effective as pethidine, 50 mg, in the alleviation of pain, though the initial dose had to be higher. Nausea and vomiting were half as frequent in the levomepromazine group as in the pethidine group (p less than 0.001). The incidences of arrhythmias, lung oedema, hypotension and thromboembolic complications did not differ between the groups. The mortality rate in the first 4 weeks was 22% in the levomepromazine group and 37% in the pethidine group (p less than 0.005), and after one year 39 and 50% (p less than 0.05), respectively. It is concluded that levomepromazine is better tolerated than pethidine in AMI. This suggests that the present management of pain in AMI should be reconsidered.

Acute Disease↗