SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
In a randomized trial, three alternative schemes of treatment of preterm labour with ritodrine (long infusion, short infusion, and intramuscular injection) were compared with standard treatment by bed rest and sedatives. None of the ritodrine treatments were found to be better in postponing delivery than the standard treatment. However, the Bishop scores of the patients in the standard treatment group tended to be lower than of the patients treated with ritodrine. Moreover, all cases of congenital malformation and polyhydramnios occurred in the patients treated with ritodrine. The incidence of respiratory insufficiency was significantly higher in infants of mothers treated with ritodrine. The mean birth weight was highest in the standard treatment group.
A sustained-release administration form of oral ritodrine was introduced to cope with the problem of the short dosage interval inherent to conventional oral ritodrine administration. The bioavailability of this application form was assessed in a clinical study including 11 patients. With a dosage frequency of only 3 times daily and a dosage form index of 1.8, plasma levels of 14.6-26.5 ng/ml ritodrine (equivalent to an infusion rate of approximately 50 micrograms/min) were obtained without serious cardiovascular or metabolic side effects. It was concluded that with this new formulation clinical applicability of orally administered ritodrine in tocolytic therapy has increased.
The purpose of this study was to determine whether prior administration ritodrine worsens maternal hypotension during epidural anesthesia in gravid ewes. Twenty-four experiments were performed in nine chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included the following: 1) at time-zero, intravenous (iv) administration of ritodrine, 0.004 mg.kg-1.min-1, or normal saline (NS) for 2 h; 2) at 120 min discontinuation of ritodrine, and administration of a 500 ml iv bolus of NS over 15 min; and 3) at 135 min epidural injection of 2% lidocaine or NS. There were three groups of experiments: 1) iv ritodrine-epidural lidocaine (n = 9); 2) iv NS-epidural lidocaine (n = 8); and 3) iv ritodrine-epidural NS (n =7). Epidural injection of lidocaine resulted in a median sensory level of T9 in both the ritodrine-lidocaine and NS-lidocaine groups. At 165 min (i.e., 30 min after the epidural injection of lidocaine), maternal mean arterial pressure was 19 +/- 3% below baseline (P = 0.0001) in the ritodrine-lidocaine group and 22 +/- 7% below baseline (P = 0.0001) in the NS-lidocaine group (NS between groups). At 120 min ritodrine had increased maternal cardiac output 45 +/- 6% above baseline (P = 0.0001) in the ritodrine-lidocaine group and 39 +/- 6% above baseline (P = 0.0001) in the ritodrine-NS group. Cardiac output remained above baseline (P less than 0.01) after epidural injection of lidocaine in the ritodrine-lidocaine group. In contrast, in the NS-lidocaine group cardiac output was 13 +/- 5% below baseline (P = 0.005) at 150 min. Fetal arterial pH did not change significantly in either the ritodrine-lidocaine or ritodrine-NS group.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacological effects of ritodrine hydrochloride (ritodrine), a beta 2-adrenoceptor agonist, were investigated in comparison with that of isoxsuprine hydrochloride (isoxsuprine) on the motor nervous system and the central nervous system. Ritodrine (1-30 mg/kg, i.v.) suppressed spontaneous movements in mice, rats and dogs. The animals became slightly sedative and immobile. Ritodrine caused an increase of water intake and vomitting in dogs. These fingings were recovered in 3-5 hr. Isoxsuprine showed similar effects on general behaviour, but the depressive action was more potent than that of ritodrine. Ritodrine slightly suppressed exploratory behaviour in high dose, but had little effect on emotional behaviour. Ritodrine had no effects on conditioned avoidance response, tremor, motor coordination, thiopental induced sleeping time and few types of convulsions. Ritodrine showed no analgetic effects or muscle relaxant actions. Isoxsuprine, in high dose, suppressed motor coordination and showed ataxia. Ritodrine slightly raised body temperature and dose-dependently suppressed hypothermia and ptosis induced by reserpine. Ritodrine (1-10 mg/kg, i.v.) caused a slight resting pattern of spontaneous EEG in rabbits. On the other hand, arousal responses evoked by auditory stimulation, photic stimulation or electrical stimulation of mesencephalic reticular formation were unaffected by ritodrine at any doses used. These results suggest that ritodrine shows little effect on the motor nervous system and central nervous system, and its effects may be nonspecific.
A randomized controlled study was carried out at three medical centers to compare the efficacy and side effects of ethanol and ritodrine in the treatment of threatened premature labor. One hundred and thirty-five patients judged to be between the twentieth and thirty-sixth week of gestation and presenting with clinical symptoms of premature labor were included. Sixty-seven patients were treated with intravenous infusion of 10 per cent ethanol. Sixty-eight patients were treated with intravenous infusion of ritodrine for 12 hours followed by oral ritodrine. If labor recurred prematurely, up to two additional courses of ethanol or ritodrine were given. Delivery was postponed for more than 72 hours in 49 of 67 patients (73 per cent) with ethanol and in 61 of 68 patients (90 per cent) with ritodrine; this difference was significant. Patients in the ethanol group gained a mean of 27.6 days while patients in the ritodrine group gained a mean of 44.0 days. Fifty-four per cent of the ethanol group and 72 per cent of the ritodrine group carried their infants to 36 weeks of gestation. Five infants in the ethanol group and one infant in the ritodrine group died from respiratory distress syndrome. The most frequent side effect of ethanol were nausea and vomiting. The most frequent side effects of ritodrine were tachycardia and blood pressure changes which were easily controlled by lowering the infusion rate. Ethanol and ritodrine were both found to be effective inhibitors of premature labor with ritodrine giving the most favorable results.
The oral dosing regimen for ritodrine was based in large part on kinetic data obtained in nonpregnant subjects. There are limited kinetic data after oral administration of ritodrine in pregnancy. The purpose of the present study was to compare ritodrine kinetics in pregnant and nonpregnant women, evaluate the effect of feeding on ritodrine absorption in pregnant women, and determine if the plasma concentration of ritodrine is proportional to the dose administered in nonpregnant women. Plasma concentrations after a single 20 mg dose of ritodrine were significantly greater in fasting nonpregnant women than in fasting pregnant women. The area under the concentration time curve was 1372 +/- 385 and 1001 +/- 257 ng/ml/min, respectively. In pregnant women ingesting 20 mg of ritodrine, plasma concentrations were not significantly different in the fed or fasted state; plasma concentrations peaked at 11 ng/ml and were less than 3 ng/ml within 4 hours. In nonpregnant subjects the concentration of ritodrine in plasma was proportional to the dose. After ingestion of 10, 20, or 30 mg of ritodrine, the area under the curve was 751 +/- 253, 1372 +/- 385, and 2148 +/- 571 ng/ml/min, respectively. These data indicate that ritodrine concentrations in pregnant women after a 20 mg oral dose are low. Increases in dosage will probably result in proportional increases in plasma concentration. The maximal dose of ritodrine recommended for prevention of recurrent preterm labor should be increased.
The ability of the human fetus and neonate to conjugate and excrete ritodrine, a beta 2-sympathomimetic drug, was investigated. Free and conjugated ritodrine concentrations in the plasma, amniotic fluid and urine were measured in 11 mother-infant pairs, to whom intravenous ritodrine had been administered before elective cesarean section at term. Ritodrine was determined by HPLC with electrochemical detection. At delivery, conjugated ritodrine values were significantly higher than those for the free form in maternal and fetal plasma. There were significant positive correlations between the concentrations in the maternal and umbilical vein plasma for both free and conjugated ritodrine. In the amniotic fluid, the total ritodrine concentrations were much higher than those in the fetal plasma, the conjugated form accounting for 90.2% of the total. Furthermore, the percentages of conjugated ritodrine in the amniotic fluid and neonatal urine were significantly higher than the percentage in the maternal urine on the day of birth. In the neonatal urine, the concentrations of free and conjugated ritodrine decreased rapidly after birth as did those in the maternal urine, on day 3 postpartum being less than 2% of the values on the day of parturition. These results indicate that the fetus at term is capable of forming conjugated metabolites of ritodrine and of excreting free and conjugated ritodrine in its urine.
In this study we compare the uterine contractility and beta-adrenergic receptor effects of identical doses of ritodrine administered intermittently or continuously for 24 hours in pregnant sheep. Ritodrine was administered intravenously to five animals as a pulse, 16 micrograms/kg every 1.5 hours, whereas five other animals received ritodrine as a continuous infusion of 0.18 microgram/kg/min. Ritodrine plasma concentrations at steady state were comparable in both groups and averaged 18 ng/ml. Animals receiving ritodrine pulses demonstrated no alteration of myometrial beta-adrenergic receptors or adenylyl cyclase activity, and ritodrine inhibited oxytocin-induced contractility comparably at 4 and 24 hours. Animals receiving ritodrine continuously had a significant decrease in myometrial beta-adrenergic receptors and adenylyl cyclase activity, yet ritodrine inhibition of oxytocin-induced uterine contractility was sustained for 24 hours. Oxytocin receptors were not affected by ritodrine administration and were similar in both groups. At the dose studied, oxytocin-induced contractions are comparably inhibited by ritodrine for 24 hours whether the drug is given continuously or in a pulsatile fashion.
OBJECTIVE: Our aim was to compare plasma drug levels in patients receiving ritodrine intravenously with those in patients receiving ritodrine orally at recommended dosages. STUDY DESIGN: Plasma samples from 20 pregnant patients treated with intravenous ritodrine (50 to 300 micrograms/min), 9 patients treated with oral ritodrine only (60 to 120 mg per 24 hours), and 9 patients treated first with intravenous and subsequently with oral ritodrine were analyzed for ritodrine concentration with the use of high-performance liquid chromatography. RESULTS: Average plasma ritodrine levels of patients receiving different intravenous dosages ranged from 27.8 +/- 3.5 to 113.3 +/- 38.8 ng/ml. Levels during oral therapy ranged between 9.8 +/- 3.2 and 13.8 +/- 4.4 ng/ml. In both modes of drug delivery, concentrations were significantly correlated with doses. In patients treated first with intravenous ritodrine and subsequently with the oral form, plasma concentrations during oral therapy averaged 27.7% +/- 18.8% of those obtained during intravenous infusion. CONCLUSION: Subtherapeutic plasma concentrations might be responsible for the failure to demonstrate clinical benefits of oral ritodrine in prevention of recurrent preterm labor. A twofold to threefold increase in the maximum recommended oral dosage of ritodrine should be considered, especially for patients who had previously required relatively high intravenous infusion rates (> 100 micrograms/min).
OBJECTIVE: We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo. STUDY DESIGN: We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embryo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine. RESULTS: Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine induced significantly more anomalies at or above doses of 4.6 x 10(-9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutaline's potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine. CONCLUSIONS: Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.
Ritodrine hydrochloride (ritodrine) is a beta 2-adrenoceptor stimulant which has been effectively prescribed for the prevention of premature labor. The present studies were carried out to investigate the effects of ritodrine on uterine motility in rats and rabbits during gestation, as compared with those of isoproterenol and isoxsuprine. The results were as follows: 1) Spontaneous movements and evoked contractile responses of isolated rat uterus (19-20th days of gestation) were suppressed by 10(-9) - 10(-6) M ritodrine. The potency of ritodrine was approximately 10 times more than that of isoxsuprine and 100 - 1,000 times less than that of isoproterenol. 2) When these drugs were administered to pregnant rats or rabbits intravenously, the tocolytic potency was in the following order: isoproterenol greater than ritodrine greater than isoxsuprine. 3) Ritodrine induced hypotension and tachycardia, but these effects were less than those of isoproterenol and isoxsuprine. 4) The effects of isoproterenol and ritodrine were almost prevented by pretreatment with propranolol, but those of isoxsuprine were only partially or not affected. These results suggest that ritodrine is effective in preventing the uterine contractions in rats and rabbits and that it has less effect on the circulatory system than isoproterenol and isoxsuprine. It is also concluded that ritodrine produces these effects through activation of beta-adrenoceptors.
Seventy-four patients in preterm labor at 20-35 weeks' gestation were randomly assigned to receive ritodrine (N = 36) or ritodrine plus magnesium sulfate treatment (N = 38) for tocolysis. Ten did not complete therapy and were excluded from analysis. Nineteen of 32 patients (59%) in the ritodrine plus magnesium sulfate group were successfully treated, compared with only 11 of 32 patients (34%) in the ritodrine-only group (P less than .05). Of the 21 patients who failed to respond to the initial ritodrine treatment, 16 received intravenous magnesium sulfate supplemental therapy; 75% of this group were treated successfully. The frequency of adverse maternal and fetal side effects did not differ between the treatment groups. In the combined group compared with the ritodrine group, the dose requirements for ritodrine therapy as well as the total duration of treatment for both ritodrine and magnesium sulfate were reduced significantly. We conclude that concurrent administration of ritodrine and magnesium sulfate is more efficacious than ritodrine alone and does not appear to increase the frequency of adverse side effects.
Ritodrine hydrochloride (ritodrine) is a beta 2-adrenoceptor agonist and has been effectively prescribed for the prevention of premature labor. The present study was carried out to investigate the effect of ritodrine on uterine motility, cardiovascular system, fetal heart rate and placental blood flow in late pregnant rabbits, in comparison with the effects of isoproterenol and isoxsuprine. Furthermore, we investigated the effect of ritodrine on the damage to utero-placental circulation evoked by drugs. Ritodrine (10-1,000 micrograms/kg) suppressed the spontaneous motility of pregnant rabbit uterus (27-29th days of gestation) in a dose-dependent manner. Maternal blood pressure and heart rate were little affected by ritodrine. Isoxsuprine induced hypotension and isoproterenol increased the heart rate. Ritodrine and isoproterenol had little effect on the fetal heart rate. On the other hand, isoxsuprine induced marked fetal bradycardia. Ritodrine, isoxsuprine and isoproterenol showed a tendency to decrease the placental blood flow. Isoxsuprine was more potent than the other two drugs and needed a long time for restoration. Ritodrine restored the changes in placental blood flow or fetal heart rate evoked by drugs. These results suggest that ritodrine effectively suppresses uterine motility and has little effect on the maternal land fetal cardiovascular system.
We have previously demonstrated in pregnant sheep that ritodrine infusion for 24 hours reduces myometrial beta-adrenergic receptor density and isoproterenol-stimulated adenylate cyclase activity. These receptor-associated changes were accompanied by an increasing inability of ritodrine to inhibit uterine contractility induced by a bolus of oxytocin. In the present study, we evaluated whether these ritodrine-induced effects could be altered by dexamethasone. Ten pregnant sheep at gestational ages of 92 to 130 days received ritodrine 2 micrograms/kg/min for 24 hours. Five animals also received dexamethasone 10 mg intravascularly twice during the ritodrine infusion. Before and at 4 and 24 hours of ritodrine infusion, the animals were given an identical dose of oxytocin as a bolus, and the area under the uterine pressure-time curve was quantified. Myometrial biopsy specimens were obtained before and after ritodrine infusion. Dexamethasone treatment prevented ritodrine-induced reductions in beta-adrenergic receptor density and isoproterenol-stimulated adenylate cyclase activity. Despite these receptor-associated effects, dexamethasone did not prevent the loss of tocolytic efficacy associated with prolonged ritodrine infusion.
To define the pharmacokinetics and pharmacodynamics of ritodrine after intramuscular injection, we administered 5 or 10 mg ritodrine into the gluteus or deltoid muscles of 12 pregnant volunteers. Six women received 5 mg and six received 10 mg into each muscle group on different days. We withdrew blood samples before and 12 times in the 6 hours after ritodrine injection. Blood pressure and heart rate were recorded at each time. Ritodrine was measured by high-performance liquid chromatography. Peak ritodrine concentrations (mean +/- SD) after a single 5 mg injection in the deltoid or gluteus were 38 +/- 13 and 26 +/- 8 ng/ml, respectively. After a 10 mg dose in the deltoid or gluteus, peak concentrations were 59 +/- 30 and 47 +/- 22 ng/ml, respectively. Although higher, the peak plasma concentrations after injections into the deltoid were not significantly greater than those after injection into the gluteus. None of the pharmacokinetic parameters differed according to dose or injection site. The pharmacodynamic effects of ritodrine were unaffected by injection site, but ritodrine caused a dose-related increase in heart rate and systolic blood pressure and a dose-related decrease in diastolic blood pressure. After a 10 mg injection, the maximal changes in heart rate, systolic, and diastolic blood pressure were 22%, 10%, and 19%, respectively. However, mean blood pressure was not altered by either the 5 or 10 mg dose. These findings indicate that there are few differences in pharmacokinetic parameters between deltoid and gluteal injection of ritodrine. The single intramuscular injection of 5 or 10 mg ritodrine results in labor-inhibiting concentrations with clinically insignificant cardiovascular effects.
Placental transfer of ritodrine hydrochloride (ritodrine) was investigated in late-pregnant women following continuous infusion. Five volunteer women undergoing cesarean section received a total dose of 650-5970 mg of ritodrine for 8-49 days. After the infusion was discontinued at cesarean section, maternal and fetal blood and amniotic fluid were collected for later determinations of ritodrine by radioimmunoassay. Maternal serum concentrations of ritodrine were between 99.0-332.4 ng/ml. Serum levels of ritodrine in cord artery and vein were 75.9-250.5 ng/ml and 74.7-213.0 ng/ml, respectively. Ritodrine levels in amniotic fluid ranged from 126.0 to 424.0 ng/ml. The concentration of ritodrine in cord vein to maternal vein (CV/MV) was 0.695 +/- 0.066 (m +/- SE), while the concentration ratio of the amniotic fluid to maternal vein (AF/MV) was 1.719 +/- 0.211. In the present study of continuous administration of ritodrine, remarkably higher concentrations in fetal circulation and amniotic fluid were observed compared to those in cases of short-term infusion.
The purpose of the study was to determine if the adjunctive administration of magnesium sulfate with ritodrine would result in decreased dosage requirements of ritodrine, and, therefore, decrease the incidence of ritodrine-associated side effects. Candidates for tocolysis were prospectively randomized so that some received a uniform tocolytic dose of magnesium sulfate in a blinded protocol. All patients received a ritodrine infusion which was titrated in the standard manner to achieve cessation of labor. Evaluations included interval cumulative ritodrine dose, maximal ritodrine infusion rate, fluid balance, and blood chemistry studies. Contrary to our hypothesis, there were significantly more cardiovascular effects in the group that received ritodrine plus magnesium sulfate (11/24) than in the group that received ritodrine alone (1/17) (p less than or equal to 0.02). The predominant side effect was chest pain, frequently associated with electrocardiogram changes indicative of myocardial ischemia. These results are consistent with the current understanding of the regulatory mechanisms of these tocolytic agents. We conclude from the results of our prospective, randomized, blinded study that the adjunctive use of magnesium sulfate with ritodrine is associated with an unacceptable increase in serious side effects and probably does not improve efficacy.