RESUMEN
PURPOSE: To evaluate the effect of the anti-cancer drug carboplatin on plasma concentrations and urinary excretion of L-carnitine (LC) and its main ester, acetyl-L-carnitine (ALC), in cancer patients. METHODS: Plasma and urine concentrations of LC and ALC from 11 patients on carboplatin therapy (1 h intravenous infusion; AUC dose 4.8 +/- 1.1 mg/ml min) in combination with docetaxel, paclitaxel or vinorelbine, were determined by high-performance liquid chromatography with fluorimetric detection. RESULTS: Before carboplatin therapy, the mean +/- SD plasma concentrations of LC and ALC were 47.8 +/- 10.9 and 7.04 +/- 1.04 nmoles/ml, respectively, and remained constant throughout the entire study period. In contrast, urinary excretion of LC and ALC, increased significantly during the chemotherapy from 115 +/- 105 to 480 +/- 348 micromoles/day (P < 0.01) and from 41 +/- 41 to 89 +/- 52 micromoles/day (P < 0.05) for LC and ALC, respectively, subsequently reverting to normal 6 days after the end of chemotherapy. Similarly, the renal clearance of LC and ALC increased substantially during chemotherapy from 1.67 +/- 1.43 to 9.05 +/- 9.52 ml/min (P < 0.05) and from 4.02 +/- 4.51 to 7.97 +/- 5.05 ml/min (P = not significant) for LC and ALC, respectively, reverting to normal 6 days after the end of chemotherapy. Plasma concentrations and urinary excretion of glucose, phosphate and urea nitrogen and creatinine clearance, however, were not affected by carboplatin therapy, indicating no impaired kidney function. CONCLUSION: Treatment with carboplatin was associated with a marked urinary loss of LC and ALC, most likely due to inhibition of carnitine reabsorption in the kidney.
Asunto(s)
Acetilcarnitina/orina , Carboplatino/uso terapéutico , Carnitina/orina , Neoplasias/tratamiento farmacológico , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Carboplatino/administración & dosificación , Carboplatino/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Creatinina/orina , Docetaxel , Femenino , Glucosa/metabolismo , Humanos , Infusiones Intravenosas , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Neoplasias/orina , Paclitaxel/administración & dosificación , Fosfatos/orina , Taxoides/administración & dosificación , Urea/orina , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
Carnitine is a trimethylamine molecule that plays a unique role in cell energy metabolism. Mitochondrial betaoxidation of long-chain fatty acids, the major process by which fatty acids are oxidized, is ubiquitously dependent on carnitine. Control of mitochondrial beta-oxidation through carnitine adapts to differing requirements in different tissues. The physiological role of carnitine and its system in body composition is understood from insights into skeletal muscle metabolism, which converge into the metabolic heterogeneity of muscle fibers, and contractile properties that are correlated with phenotypes of resistance to fatigue. In skeletal muscle, the importance of the function of the carnitine system in the control and regulation of fuel partitioning not only relates to the metabolism of fatty acids and the capacity for fatty acid utilization, but also to systemic fat balance and insulin resistance. The carnitine system is shown to be determinant in insulin regulation of fat and glucose metabolic rate in skeletal muscle, this being critical in determining body composition and relevant raised levels of risk factors for cardiovascular disease, obesity, hypertension, and type 2 diabetes.
Asunto(s)
Composición Corporal/fisiología , Carnitina/metabolismo , Animales , Homeostasis , Humanos , Resistencia a la Insulina/fisiología , Mitocondrias/metabolismo , Modelos Animales , Músculo Esquelético/metabolismo , Oxidación-ReducciónRESUMEN
Hyperactivity is a significant problem for almost all young males affected by fragile X syndrome (FXS), the most common inherited disease causing mental retardation. Therapeutical approaches are actually based on Central Nervous System (CNS) stimulants lacking a well defined rationale and efficacy while they further decrease the patient's limited attention span. A pilot study on 17 fragile X male treated with L-acetylcarnitine (LAC) over one year, showed a significant reduction of their hyperactivity behaviour tested by the Conners Abbreviated Parent-Teacher Questionnaire. LAC use in FXS patients derives from the hypothesis that the biochemical and physiological properties this substance has may preserve brain activity. LAC is a small, hydrosoluble molecule that easily diffuses in the extracellular space and enters any cell in the nervous system through specific transporters. Different cerebral areas use this molecule differently to metabolize glucose and lipids to provide for ATP and neurotrasmitters synthesis. The acetyl group LAC carriers represents a key metabolic signaling element possibly mediating its effect in the CNS. The exogenous administration of LAC may affect brain activity in FXS by: I) modulation of fuel partitioning for energy production, which at the mithocondrial level is associated with the Kreb's cycle metabolic role in neurotransmitter synthesis; II) remodelling of lipid membrane in terms of LAC actively determining the production of polyunsaturated fatty acids; III) preferential effect on the attention component of the cholinergic system which relies on its peculiar modality of communication in the CNS. Based on the above premises an explorative, double-blind, placebo controlled, multicenter study is ongoing. A total population of 160 children from nine European centers will be enrolled. The objective of this study is to determine the effect of LAC on the hyperactive behaviour of FXS children as evaluated by the administration of the Conners Abbreviated Parent Questionnaire.
Asunto(s)
Acetilcarnitina/uso terapéutico , Trastornos de la Conducta Infantil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Hipercinesia/tratamiento farmacológico , Acetilcarnitina/química , Niño , Ensayos Clínicos como Asunto , Síndrome del Cromosoma X Frágil/complicaciones , Humanos , Hipercinesia/etiología , Masculino , Estructura Molecular , Pruebas Neuropsicológicas , Proyectos PilotoRESUMEN
The hemodynamic effect of L-propionylcarnitine (LPC) administered intravenously was evaluated in a double-blind, randomized, three-period crossover study in 12 men (aged sixty to seventy-five years) with Leriche-Fontaine stage II peripheral arterial disease of lower limbs. At baseline, maximum working capacity of each patient was determined by a standardized ergometric test. This test was repeated at 80% of each patient's maximum working capacity before and after intravenous administration of LPC. Each patient received three single doses of 300 mg, 600 mg, and 1200 mg of LPC with a two-day rest period between them. Hemodynamic variables measured by strain-gauge plethysmography were: peak blood flow, peak flow time, and halftime and total time of hyperemia both after exercise and after induction of ischemia (with an occlusion cuff). LPC administration significantly shortened the halftime as well as the total time of hyperemia after exercise and after ischemia. With the two highest doses, LPC shortened the peak flow time after exercise. The peak blood flow after exercise and after ischemia increased, but this increase did not reach statistical significance. The results obtained indicate that LPC improves circulatory reserve of the ischemic limb and has no effect on heart rate and arterial blood pressure. No adverse events were reported. The effect of LPC on the hyperemic response to stress, mainly on halftime of hyperemia, is possibly due to a drug-induced increase of adenosine triphosphate utilization by the ischemic tissues.
Asunto(s)
Carnitina/análogos & derivados , Hiperemia/fisiopatología , Claudicación Intermitente/tratamiento farmacológico , Pierna/irrigación sanguínea , Esfuerzo Físico , Anciano , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Carnitina/administración & dosificación , Carnitina/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Humanos , Hiperemia/etiología , Inyecciones Intravenosas , Claudicación Intermitente/fisiopatología , Isquemia/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
Biopsies were taken from the vastus lateralis muscle of 26 chronic uremic patients before and after a 24-week treatment with L-carnitine given at the dose of 2 g i.v. at the end of hemodialysis, or in dialysis solution, or per os twice daily. The aim of the study was to evaluate both the muscle morphology in dialyzed subjects and the modification provoked by the therapy. All patients manifested a significant, even if variable, degree of muscular atrophy which involved all types of muscle fibers. After the treatment there was an increase of about 7% in the diameter of type I and type IIa fibers, which can utilize carnitine for fatty acid oxidation to produce energy, and a reduction in the atrophic fibers. No noteworthy changes were documented in type IIb fibers, which depend on glycolysis for energy production.
Asunto(s)
Carnitina/uso terapéutico , Músculo Esquelético/efectos de los fármacos , Uremia/tratamiento farmacológico , Carnitina/sangre , Carnitina/metabolismo , Metabolismo Energético/efectos de los fármacos , Femenino , Humanos , Hipertrofia , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/patología , Atrofia Muscular/prevención & control , Diálisis Renal , Seguridad , Uremia/patología , Uremia/fisiopatologíaRESUMEN
Plasma concentration, urinary excretion and renal clearance of free, total and esterified L-carnitine were monitored monthly in 14 women during the last 6 months of pregnancy and 1 month after delivery. Plasma concentration and renal clearance measured 1 month after delivery overlapped with normal values for females of comparable age, and were considered the reference values for further comparisons. Plasma concentration of free, total and esterified L-carnitine decreased during pregnancy, reaching values as low as half of those measured 1 month after delivery, whereas urinary excretion and renal clearance, mainly of L-carnitine esters, increased, with renal clearance reaching a peak at the 16th week of pregnancy. Pregnancy thus leads to a reversible secondary deficiency of L-carnitine. The involvement of L-carnitine in the excretion of an excess of acyl-S-coenzyme A groups to prevent a possible systemic acidosis, as well as hormonal changes and a reduction of L-carnitine biosynthesis, could play a significant role in the variations in L-carnitine metabolism encountered in pregnancy. As physiological components of L-carnitine are excreted via a saturable tubular reabsorption, their threshold seems to follow plasma concentration, even when they decrease markedly, as in pregnancy.
Asunto(s)
Carnitina , Riñón/metabolismo , Primer Trimestre del Embarazo/metabolismo , Adolescente , Adulto , Análisis de Varianza , Carnitina/sangre , Carnitina/deficiencia , Carnitina/orina , Femenino , Humanos , EmbarazoRESUMEN
The effects of L-carnitine on respiratory chain enzymes in muscle of long distance runners were studied in 14 athletes. These subjects received placebo or L-carnitine (2 g orally b.i.d.) during a 4-week period of training. Athletes receiving L-carnitine showed a significant increase (p < 0.01) in the activities of rotenone-sensitive NADH cytochrome c reductase, succinate cytochrome c reductase and cytochrome oxidase. In contrast, succinate dehydrogenase and citrate synthase were unchanged. No significant changes were observed after placebo administration. The levels of both total and free carnitine from athletes receiving placebo were significantly decreased (p < 0.01) after treatment. By contrast, total and free carnitine levels were markedly increased (p < 0.01) after supplementation with L-carnitine. Our results suggest that L-carnitine induces an increase of the respiratory chain enzyme activities in muscle, probably by mechanisms involving mitochondrial DNA.
Asunto(s)
Carnitina/farmacología , Músculos/enzimología , Resistencia Física , Deportes , Análisis de Varianza , Carnitina/metabolismo , Citrato (si)-Sintasa/metabolismo , Complejo II de Transporte de Electrones , Complejo III de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Ingestión de Energía , Humanos , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/enzimología , Complejos Multienzimáticos/metabolismo , Músculos/efectos de los fármacos , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Oxidorreductasas/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Succinato Deshidrogenasa/metabolismoRESUMEN
Efficient utilization of fatty acids to sustain prolonged physical efforts is thought to be dependent on the carnitine shuttle of muscle. A study has been carried out in 24 athletes (13 long-distance runners and 11 sprinters). These subjects received placebo or L-carnitine (1 g/orally b.i.d.) during a 6-month period of training. In endurance athletes, training induced lowering of total and free muscle carnitine. Increase of esterified muscle carnitine was also observed. Post-exertional overflow of acetylcarnitine and long-chain acylcarnitine, as well as reduction of the free fraction was also noticed in the blood. Fasting plasma carnitine levels, however, were not affected in carnitine-treated athletes at rest. These changes were likely related with the significantly increased urinary excretion of esterified and total carnitine which occurred after physical exercise. In the sprinters only, a decrease in free and total carnitine of muscle was detected after training. Both these potentially unfavorable effects were prevented by oral administration of L-carnitine. Our data suggest that training in endurance athletes, and to a lesser extent, in sprinters, is associated with a decrease in free and total carnitine of muscle, due to an increased overflow of short-chain carnitine esters in urine.
Asunto(s)
Carnitina/análisis , Carnitina/farmacología , Ejercicio Físico/fisiología , Músculos/química , Educación y Entrenamiento Físico , Adulto , Carnitina/fisiología , Femenino , Humanos , Masculino , Resistencia Física/fisiología , CarreraRESUMEN
The clinical use of acetyl carnitine in circulatory shock has its theoretical basis in the ability of this molecule to restore enzyme activity inhibited by hypoxia, acting as an acetyl donor. Moreover the action of carnitine on an injured myocardium encouraged us to examine the clinical effect of this drug during heart failure. A double-blind clinical study was performed in ten Italian intensive care units on 115 patients with septic, cardiac of traumatic shock, by using acetyl-L-carnitine infusion for 12 hours, with a previous single bolus intravenously. The results showed a good response to the drug in terms of blood oxygenation during the course of sepsis and heart failure. The heart rate as well as right atrial pressure decreased significantly in patients with cardiogenic shock. In septic patients systolic and mean arterial pressures increased also. The present data suggests the use of acetyl-L-carnitine as an adjuvant to the commonly used therapy in hypoxic conditions.
Asunto(s)
Acetilcarnitina/uso terapéutico , Choque/tratamiento farmacológico , Acetilcarnitina/administración & dosificación , Adolescente , Adulto , Anciano , Monitores de Presión Sanguínea , Método Doble Ciego , Hemodinámica/efectos de los fármacos , Humanos , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Persona de Mediana Edad , Choque Cardiogénico/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Choque Traumático/tratamiento farmacológico , Tasa de SupervivenciaRESUMEN
It has been reported that treatment with L-carnitine at a daily dose of 3 g orally may cause a rise in platelet aggregation and serum triglyceride concentration in hemodialyzed patients. The present double-blind cross-over study has been performed to evaluate the influence of L-carnitine when compared with placebo on platelet aggregation and plasma concentrations of various factors involved in platelet activation. In addition, the concentration of triglycerides, cholesterol and HDL-cholesterol has been evaluated. 18 uremic patients on maintenance hemodialysis for at least 1 year were randomly allocated either to a control group receiving placebo or to a group treated with L-carnitine. Statistical analysis performed by means of ANOVA did not show any significant change in the serum concentration of cholesterol, HDL-cholesterol and triglycerides. Furthermore, platelet aggregation tests (performed with adenosine 5'-diphosphate, epinephrine, thrombin and collagen) and plasma beta-thromboglobulin concentration did not show any statistically significant difference. In addition, the plasma concentration of several coagulation markers, such as factor VIIIc, antithrombin III, alpha 2-antiplasmin, and fibrinopeptide A, did not show any significant variation. The results suggest that under our experimental conditions L-carnitine neither increases the risk of thromboembolism nor alters the serum lipid content in uremic patients on chronic hemodialysis.
Asunto(s)
Carnitina/farmacología , Agregación Plaquetaria/efectos de los fármacos , Diálisis Renal , Uremia/terapia , Adulto , Carnitina/administración & dosificación , Carnitina/deficiencia , Método Doble Ciego , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal/efectos adversos , Tromboembolia/etiología , Uremia/sangre , Uremia/tratamiento farmacológico , beta-Tromboglobulina/metabolismoRESUMEN
An experimental model was developed to investigate some metabolic effects of strenuous exercise in hypoxic muscle tissue of human volunteers. The incidence of carnitine supplementation was studied, assuming as marker the thiobarbituric acid reaction products analysed in plasma samples collected during the course of the protocol programme. Propionyl-L-carnitine appears to antagonize in a significant degree the damaging effects of muscle fatigue combined with hypoxic status. Under these conditions the detoxifying role played by propionyl-L-carnitine, previously reported in various tissues and in other pathological conditions, appears to be relevant, although further studies are needed to elucidate the pharmacodynamics of this molecule.
Asunto(s)
Carnitina/análogos & derivados , Carnitina/farmacología , Músculos/metabolismo , Esfuerzo Físico , Carnitina/metabolismo , Humanos , Hipoxia/tratamiento farmacológico , Hipoxia/etiología , Peróxidos Lipídicos/sangre , Músculos/efectos de los fármacos , Factores de TiempoRESUMEN
We investigated the effect of long-term i.v. administration of L-carnitine on human muscle fibers using morphometric parameters. We administered 2g/day L-carnitine to patients undergoing hemodialysis for at least 12 months. At the end of this period a marked increase in serum and muscle carnitine levels was observed in all patients, together with hypertrophy and predominance of type 1 fibers. L-carnitine was withheld for 4 months, during which time serum and muscle levels gradually decreased and no changes were observed in muscle fibers. Subsequent addition of L-carnitine to dialysis fluid for another 4 months stabilized lower levels. At the end of this period reduction of diameter of type 1 fibers was observed. Type 2 fibers remained unchanged. Moreover, type 1 fibers remained predominant in all cases. Hence, we suggest that carnitine has a specific trophic effect on type 1 fibers which are characterized by an oxidative metabolism.
Asunto(s)
Carnitina/farmacología , Músculos/efectos de los fármacos , Anciano , Carnitina/deficiencia , Carnitina/metabolismo , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Músculos/metabolismo , Músculos/patología , Atrofia Muscular/etiología , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Diálisis Renal/efectos adversos , Uremia/metabolismo , Uremia/patología , Uremia/terapiaRESUMEN
L-Carnitine has been reported to have beneficial effects in the reduction of serum triglycerides and increases high-density lipoprotein cholesterol in hemodialysis patients. The published reports are, however, equivocal. Paradoxical increases in serum triglycerides following intravenous administration of L-carnitine have been observed. It has been suggested that the paradoxical rise in triglycerides may result from the high doses used and intravenous administration, both of which may cause abnormally high tissue concentrations. In the present study 22 hemodialysis patients were selected. All patients had been treated intravenously with 2 g of L-carnitine administered at the end of dialysis for a minimum of 12 months. Treatment with L-carnitine was then discontinued during a 4-month washout period. The patients were then divided into two equal subgroups and placed on L-carnitine therapy (1 g i.v.) at the end of dialysis for 1 month. Thereafter, L-carnitine was added to the dialysate (2 g in group 1, 4 g in group 2) for 3 months. Serum and muscle carnitine levels were determined throughout the study as were lipid parameters, serum chemistry, and hematology. Muscle biopsies obtained at baseline revealed supranormal levels of carnitine which decreased to normal levels following the 4-month washout period. When therapy with L-carnitine was resumed, intravenous administration or in dialysate, the muscle carnitine levels remained within the normal range. Similarly, serum carnitine was markedly elevated at baseline and decreased to normal during the washout period. When L-carnitine was added to the dialysate, total carnitine was observed to significantly increase in the group receiving 4 g.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Carnitina/uso terapéutico , HDL-Colesterol/sangre , Soluciones para Diálisis/uso terapéutico , Músculos/metabolismo , Diálisis Renal , Triglicéridos/sangre , Anciano , Carnitina/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To 6 healthy volunteers 30 mg/kg of L-carnitine (1,3-hydroxy-4-N-trimethylamino-butyrate) were injected intravenously and plasma levels (mumol/l) of free and short-chain carnitine were determined at different times between 0.033 and 24 h. The urinary excretion of L-carnitine and short-chain carnitine in 24 h was also measured. After a period of wash-out the subjects received 100 mg/kg of L-carnitine orally and plasma levels were determined between 0.5 and 24 h. The urinary excretion of L-carnitine was measured for a period of 18.5-33 h after treatment. 3 of the volunteers also received 30 mg/kg of L-carnitine orally. Carnitine plasma levels were determined at different times between 0.5 and 18 h, while the urinary excretion of L-carnitine was measured for 48 h following the treatment. The results could indicate the presence of saturation phenomena in the absorption process for the oral doses used; specific research is required to ascertain this phenomena. The transfer of carnitine from central to extravascular volume is relatively rapid, as is its urinary excretion. The short half-life of carnitine and acetyl-carnitine can suggest the use of new forms of administration (slow-release).
Asunto(s)
Carnitina/farmacocinética , Administración Oral , Adulto , Carnitina/sangre , Carnitina/orina , Humanos , Inyecciones Intravenosas , Masculino , Modelos BiológicosRESUMEN
The effects of chronic administration of L-carnitine were evaluated by EMG analysis in 20 uraemic patients undergoing periodical haemodialysis (mean duration of dialysis 34.7 months). No important changes in motor conduction velocity or distal latency of the external popliteal nerve were found after the treatment, while a reduction in the number of polyphasic muscle action potentials was observed. After carnitine administration, an increase of total EMG power was noted and the spectral array showed a progressive shift towards lower frequencies in 8 patients who had shown higher values. These results suggest that carnitine has a prevalent "myotrophic" effect.
Asunto(s)
Carnitina/farmacología , Fallo Renal Crónico/fisiopatología , Músculos/efectos de los fármacos , Adulto , Computadores , Electromiografía , Potenciales Evocados/efectos de los fármacos , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Músculos/fisiopatología , Diálisis Renal , Uremia/metabolismo , Uremia/fisiopatologíaRESUMEN
The relationship between plasma carnitine levels and liver regeneration was studied in 28 female rats subjected to lobectomy using the technique of Higgins and Anderson. The results show that the determination of plasma carnitine can be considered as a liver regeneration index.
Asunto(s)
Carnitina/sangre , Regeneración Hepática , Animales , Femenino , Hepatectomía , Ratas , Factores de TiempoRESUMEN
Carnitine is a selective carrier of free fatty acids from the cytoplasm to the mitochondria. Dialysed patients are chronically and progressively carnitine deficient due to loss in the dialysate. Simultaneously such patients present impaired lipid metabolism and this may provoke varied pathological conditions ranging from isolated hypertriglyceridaemia to frank forms of hyperlipoproteinaemia types IIa, IIb, and IV, and to apparently normolipaemic situations falling within a lipoprotein pattern tending to become pathological with low levels of HDL-cholesterol. In the present investigation we evaluated the effect of l-carnitine (versus placebo) on the lipid pattern in a group of apparently normolipaemic dialysed patients, but with altered coronary risk factors (HDL-cholesterol, beta:alpha lipoprotein ratio). Examinations showed no significant changes at the 15th and 30th day of placebo treatment, whereas the l-carnitine treated group displayed a statistical significant increase in HDL-cholesterol accompanied by reduced pre-beta-lipoproteins and decreased beta:alpha ratio.
Asunto(s)
Carnitina/uso terapéutico , Hiperlipidemias/prevención & control , Lípidos/sangre , Diálisis Renal , Adulto , Carnitina/farmacología , Femenino , Humanos , MasculinoRESUMEN
The antiemetic effects of domperidone in patients undergoing post-surgical cytostatic treatment for stomach and colorectal carcinoma have been evaluated. The study has been performed on 3 groups of patients treated with domperidone, metoclopramide and placebo respectively. The antiemetic activity of domperidone proved to be better than that of metoclopramide. No side effects were observed in patients treated with domperidone.