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PubMedDate not supplied

[Treatment of depression with intravenous infusions of clomipramine and maprotiline].

28 patients aged from 31 to 69 years with endogenous depression were studied. All cases were drug-resistant i.e. they did not improve after a treatment with tricyclic antidepressants and in four cases also after electroconvulsive therapy. The group were managed with intravenous infusions of clomipramine or maprotiline followed by oral administration of the drug. Clomipramine was given i.v. at doses 75-300 mg daily for 7 to 16 days and maprotiline at 75-200 mg daily for 6 to 20 days. Remission of depressive symptoms was observed in 43% of cases and the first signs of improvement were observed on tenth day of the treatment. Tolerance to both drugs given parenterally in majority of cases was satisfactory. Half of the group did not show any untoward events. The rest of the group displayed local tissue reactions, both increased and decreased blood pressure, weakness, drowsiness, anxiety, vertigo, hyperpyretic reactions. Four patients had the treatment discontinued because of local tissue reactions or increased blood pressure or hyperpyretic reactions.

Administration, Oral↗
PubMed2001

Intravenous infusion of iron and tetrahydrofolate does not influence intrauterine uteroferrin and secreted folate-binding protein content in swine.

The effect of exogenous iron and folate on reproductive performance in swine is equivocal. However, the effect of exogenous iron and folate on secretion of their respective uterine transport proteins has never been reported. Twenty gilts were infused (n = 5 per treatment) with either 1) saline, 2) alpha-tocopherol, 3) alpha-tocopherol plus iron citrate, or 4) alpha-tocopherol plus tetrahydrofolate on d 11 to 14 of pregnancy. Intravenous infusion of iron citrate and tetrahydrofolate increased (P < 0.05) plasma iron and folate, respectively, for 6 to 8 h after treatment. Treatments had no effect on uterine content of uteroferrin or secreted folate-binding protein in uterine flushings obtained on d 15 of pregnancy. These data suggest that uterine secretion of uteroferrin and secreted folate-binding protein are not influenced by plasma levels of iron and folate, respectively, and may provide an explanation for the equivocal effect of iron and folate treatment on reproductive performance in gilts.

Acid Phosphatase↗
PubMed1989

A phase I study of trimetrexate (NSC 352122) administered by 5-day continuous intravenous infusion.

Trimetrexate (TMTX) is a potent inhibitor of dihydrofolate reductase that circumvents the transport resistance seen with methotrexate and has a wide spectrum of preclinical activity. A total of 18 patients with advanced cancer were treated in a clinical and pharmacological phase I trial with TMTX given as a continuous 5-day intravenous infusion. Neutropenia, thrombocytopenia and stomatitis were the dose-limiting toxicities at the maximum tolerated dose of 50 mg/m2 per 120 h (10 mg/m2 per day for 5 days). There was one septic death associated with neutropenia. Other toxicities were mild rash, mild nausea and transiently raised serum transminase levels. Significant relationships between the dose given and the AUC of plasma TMTX and the steady-state plasma level were established. Significant, although weak, relationships between the percentage of change in neutrophils and platelets and both the AUC and steady-state plasma level of TMTX were also observed. No objective tumour responses were seen, although six patients had stable disease. The recommended phase II dose for a continuous infusion of trimetrexate is 40 mg/m2 per 120 h.

Adult↗
PubMed1999

Pharmacokinetics, safety, and tolerability of single intravenous infusions of an adenosine agonist, AMP 579, in healthy male volunteers.

The pharmacokinetics of an adenosine agonist, AMP 579, following intravenous administration were evaluated. Single AMP 579 doses of 20 to 150 micrograms/kg were infused intravenously over 6 hours using a constant-rate or two-step rate of infusion to healthy male volunteers. Plasma and urine samples were collected for measurement of AMP 579 concentration using a validated HPLC assay. An assessment of safety and tolerability was also performed. Based on a noncompartmental method of analysis, the pharmacokinetics of AMP 579 were characterized by rapid systemic clearance (0.77 to 0.85 L/h/kg), a moderate steady-state volume of distribution (0.80 to 0.94 L/kg), and a short terminal elimination half-life (0.84 to 1.13 h). AMP 579 exhibited dose (infusion rate)-proportional pharmacokinetics over the dose range. In addition, little or no unchanged AMP 579 was found in the urine. The primary cardiovascular pharmacodynamic response that was observed was a dose-related increase in mean ventricular heart rate. Fifteen minutes prior to the end of the infusion, volunteers administered the highest dose (150 micrograms/kg) exhibited a mean (range) 59% (36%-69%) increase in heart rate as compared to a mean (range) 18% (0%-73%) increase for the placebo group. No clinically relevant changes in the systolic or diastolic blood pressure were observed. The information obtained in this study should allow the design of AMP 579 dosage regimens that would maximize plasma AMP 579 concentrations and minimize the incidence of adverse events.

Adolescent↗
PubMedDate not supplied

[Continuous intravenous infusion versus intermittent administration of streptokinase in patients with deep venous thrombosis of the lower extremity].

In a multicenter randomized trial, the efficacy and safety of two streptokinase (SK) dosage regimens have been evaluated in patients with proximal deep vein thrombosis of inferior limbs. Twenty-nine patients received SK by a continuous intravenous infusion (250,000 IU as initial dose, 100,000 IU/h as maintenance dose), and 26 patients were treated with intermittent SK administration (500,000 IU as initial dose, followed by 250,000 IU every 12 h). Thrombolytic therapy was continued for 4 days, then the patients received heparin for 5 days and oral anticoagulant for 3 months. The results of treatment as judged by phlebographic examinations were similar in the two groups. Complete, substantial or partial thrombolysis was achieved in 52% of patients in the continuous infusion group and in 58% of patients in the intermittent treatment group. During SK administration, major bleeding complications occurred in 6 patients treated by continuous infusion and in 2 of the second group. The results showed that the intermittent SK administration is as effective and safe as the method of continuous SK infusion in the treatment of deep vein thrombosis.

Adolescent↗
PubMed1979

Pharmacokinetic model for procaine in humans during and following intravenous infusion.

A multicompartment pharmacokinetic model is presented to describe procaine distribution in humans during and following intravenous infusion. The model, based on a general perfusion model, relates individual characteristics such as sex, age, weight, height, infusion rate and duration, and hematocrit to general parameters such as drug metabolism, protein binding, ion-trapping effects, and tissue-plasma distribution coefficients to provide an individualized distribution prediction. Experimentally observed kinetics of blood procaine levels collected during intravenous procaine infusion as an adjunct to surgical anesthesia and blood lidocaine levels obtained from the literature compared very well with the model simulation.

Humans↗
PubMed2005

Steady-state serum concentrations of progesterone following continuous intravenous infusion in patients with acute moderate to severe traumatic brain injury.

Progesterone (PG) has been shown to provide substantial neuroprotection after traumatic brain injury (TBI) in multiple animal models. As a first step in assessing applicability to humans, the authors examined the effects of acute TBI and extracranial trauma on the pharmacokinetics of PG given by intravenous infusion. Multiple blood samples were obtained from 11 female and 21 male trauma patients receiving PG and 1 female and 3 male patients receiving placebo infusions for 72 hours. Values for C(SS), CL, t(1/2), and Vd were obtained using AUC((0-72)) and postinfusion blood samples. C(SS) values were 337 +/- 135 ng/mL, which were significantly lower than the target concentration of 450 +/- 100 ng/mL. The lower C(SS) is attributed to the CL, which was higher than anticipated. In addition, t(1/2) was longer and V(d) was higher than anticipated. These results demonstrate that stable PG concentrations can be rapidly achieved following TBI.

Area Under Curve↗
PubMed1994

Pharmacodynamics of a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) on glucose and insulin levels in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) was evaluated in 7 healthy males to determine the pharmacodynamics on glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/h over 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (p > 0.05) from their pre-dose levels. Compared to the saline (control) infusion, glucose levels were statistically lower (p < 0.05) 2 hours into the rhIGF-I infusion, and were suppressed until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. Therefore, suppression of insulin levels may be due to hypoglycemia rather than a direct action of rhIGF-I. This trial demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic or insulin resistant states.

Adult↗
PubMed1988

Salivary excretion of 5-fluorouracil. II. Fluctuation of saliva/plasma concentration ratio and salivary clearance during a constant rate intravenous infusion in beagle dogs.

Salivary excretion of 5-fluorouracil (5-FU) was investigated during constant rate intravenous infusion (0.306 mg/kg/min) in three male beagle dogs. Parotid (Pr) and mandibular-sublingual (MS) saliva were collected separately by stimulating salivation with 10% citric acid. After the start of 5-FU infusion, plasma and salivary 5-FU concentration increased rapidly to approach their steady state levels. There was a significant correlation between each saliva and plasma 5-FU concentration (p less than 0.01). The saliva/plasma drug concentration ratio (S/P ratio) and salivary pH were significantly higher in Pr than in MS saliva (p less than 0.001), similar to the results following bolus intravenous administration of 5-FU in beagle dogs. Both S/P ratio and salivary clearance increased with time before steady state. Thereafter, these values approached almost constant levels and their fluctuations became smaller than those following the bolus intravenous administration. These results showing S/P ratio and salivary clearance of 5-FU were affected by the plasma drug concentration, suggested the possibility that non-linear pharmacokinetics may be involved in the salivary excretion of 5-FU.

Animals↗
PubMed1985

Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates.

Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis.

Angiography↗
PubMed1993

Hypoglycemic and insulin response to a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) produced by expression in a yeast vector was evaluated in seven normal men to determine effects on plasma glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/hour. Each infusion lasted for 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (P > .05) from their pre-dose levels. Compared with the saline (control) infusion, serum glucose levels were statistically lower (P < .05) 2 hours into the rhIGF-I infusion. These lower glucose levels were maintained until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. This observation suggests that suppression of insulin levels may be due to secondary hypoglycemia rather than to a direct rhIGF-I effect. This study demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic states.

Adult↗
PubMed1999

Blood ammonia levels after intravenous infusion of glycine solution with and without ethanol.

OBJECTIVE: Absorption of glycine 1.5% during transurethral resection of the prostate may increase blood ammonia levels, but hyperammonaemia has not been described when the fluid also contained ethanol 1%. The aim of this experimental study was to evaluate whether ethanol 1% reduces glycine-induced hyperammonaemia. MATERIAL AND METHODS: Two intravenous infusions of glycine solution with and without ethanol 1% added were given on different occasions to 20 male volunteers (mean age 30 years). Half of them received 22 g of glycine over 50 min and the others approximately 18 g over 30 min. Blood ammonia was measured before and 30 min after the infusion. The serum levels of free amino acids were measured on 7 occasions during 10 of the experiments. RESULTS: The glycine infusions increased blood ammonia levels from 37 micromol/l (median, 10th and 90th percentile limits 34-53) to 57 micromol/l (27-110; p < 0.001). The change was greater after the larger glycine dose, regardless of whether the fluid contained ethanol (p < 0.05). The only amino acid concentration correlating with blood ammonia was glycine, which showed higher levels in those who had a rise in blood ammonia of 50% or more. CONCLUSIONS: Ethanol 1% did not reduce the increase in blood ammonia concentration after the administration of glycine solution.

Adult↗
PubMed2005

End-of-dose akinesia after a single intravenous infusion of the dopaminergic agonist piribedil in Parkinson's disease patients: a pharmacokinetic/pharmacodynamic, randomized, double-blind study.

This randomized, double-blind trial was designed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from off to on state after single intravenous infusion. Ten fluctuating patients with idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2-16 mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the motor deficit (UPDRS, motor score) including akinesia at the first evaluation time point of 15 minutes, and in reversing off state of 7 of 10 patients. The doses were equally effective, although the effect was more sustained with the highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil were not correlated to the motor score improvement or switch from off-->on. In conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and effective in improving motor symptoms, including akinesia, of fluctuating PD patients.

Aged↗
PubMed1996

Survival after high-dose intravenous infusion of irrigating fluids in the mouse.

OBJECTIVES: Fluid absorption is still a potentially fatal complication in patients undergoing transurethral resection of the prostate. We induced experimental overhydration in animals to find out which of three widely used irrigating fluids is most strongly associated with survival. METHODS: The survival and incidence of voiding was studied in 120 mice after an intravenous infusion of either 225, 250, 275, or 300 mL/kg of glycine 1.5%, mannitol 5%, or sorbitol 2% plus mannitol 1% over 60 minutes. RESULTS: Only 20% of the animals survived the glycine solution, whereas the overall survival rate after mannitol was 60%. The corresponding figure for sorbitol plus mannitol was 32%. Logistic regression analysis showed that survival was significantly more likely after infusion of mannitol 5% compared with the other irrigating fluids. The likelihood of survival was also higher in the animals in which the infusion induced diuresis and when the smaller volumes of irrigating fluid were given. CONCLUSIONS: Mannitol 5% offered the best chance of survival.

Animals↗
PubMed1993

Recombinant human gamma interferon administered by continuous intravenous infusion in acute myelogenous leukemia and myelodysplastic syndromes.

Nine patients (median age, 58; range: 37-74) with relapsed de novo acute myeloid leukemia (AML) (3), AML after prior myelodysplastic syndrome (MDS) (4), or MDS (2) were treated with 2-20 x 10(6) U/m2/day (1-10 mg/m2/day) of recombinant human interferon gamma (rIFN gamma; Biogen) on a 14-day continuous intravenous infusion schedule. The two patients who received the initial dose of 20 x 10(6) U/m2/day (1.0 mg/m2/day) could only tolerate 6 days of therapy because of severe hepatotoxicity. Two patients who received the revised starting dose of 10 x 10(6) U/m2/day also could not complete a full course of rIFN gamma due to renal failure in one case and pulmonary deterioration in the other. A reversible dose-related rise in SGOT was seen in six patients. All patients developed a severe flu-like syndrome characterized by myalgias and fevers. These toxicities were not associated with detectable serum levels of tumor necrosis factor (TNF). Although blasts from three of five assessable patients displayed increased expression of the Ia (HLA-DR) antigen, there were no hematological responses. Steady-state rIFN gamma plasma levels in patients who tolerated a complete infusion were < 40 U/ml, a concentration below that required to induce differentiation of myeloid leukemic cell lines in vitro. We conclude that continuous infusions of rIFN gamma at doses as low as 2 x 10(6) U/m2/day are poorly tolerated in patients with AML and MDS; the maximum tolerated dose is approximately 2 x 10(6) U/m2/day.

Adult↗
PubMed2001

Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes.

BACKGROUND: Levobupivacaine, the single levorotatory isomer of bupivacaine, is now available for clinical use. This study was undertaken to determine whether pregnancy affects the systemic toxicity of levobupivacaine and to compare the systemic toxicity of levobupivacaine with that of bupivacaine and ropivacaine. METHODS: Chronically prepared nonpregnant and pregnant sheep were randomized to receive an intravenous infusion of 0.52% levobupivacaine, 0.52% bupivacaine, or 0.50% ropivacaine at a constant rate of 0.1 ml x kg(-1) x min(-1) until circulatory collapse. The investigators were blinded to the identity of the local anesthetic. Physiologic parameters, including cardiac rhythm, were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations. These were analyzed for total and free serum drug concentrations as well as arterial blood pH and gas tensions. RESULTS: The doses of all three drugs required to produce convulsions were lower in pregnant than nonpregnant animals. However, as the infusion continued, there were no significant differences between pregnant and nonpregnant ewes in the dose of drug required to produce more advanced manifestations of toxicity: hypotension, apnea, and circulatory collapse. The mean cumulative dose and serum concentration at each toxic manifestation was lowest for bupivacaine, intermediate for levobupivacaine, and highest for ropivacaine in both pregnant and nonpregnant animals. For all three local anesthetics, there were no significant differences between pregnant and nonpregnant ewes in total and free serum drug concentrations, except that at circulatory collapse, these were higher in pregnant animals. CONCLUSIONS: Pregnancy increases the risk of convulsions but not of more advanced manifestations of local anesthetic toxicity. The risk of toxicity is greatest with bupivacaine and least with ropivacaine. However, in actual clinical practice, the risk of systemic toxicity may also be affected by the relative potency and effectiveness of these drugs.

Amides↗
PubMed2006

Cardiorespiratory and minimum alveolar concentration sparing effects of a continuous intravenous infusion of dexmedetomidine in halothane or isoflurane-anaesthetized rats.

Dexmedetomidine (DEX) is a highly selective alpha(2)-adrenoceptor agonist in both the central and peripheral nervous systems. Its cardiorespiratory effects have been described; however, these effects have not been reported when it is used in combination with volatile anaesthetics in rats. The cardiovascular and respiratory actions of a continuous intravenous infusion of 0.25 microg/kg/min of DEX administered to rats anaesthetized at 1 minimum alveolar concentration (MAC) of either halothane (HAL) or isoflurane (ISO) were studied. Twenty-eight rats were grouped into four treatment groups: HAL alone, ISO alone, DEX + HAL and DEX + ISO. The MAC(HAL) or MAC(ISO) was determined in each rat from alveolar gas samples at the time of tail clamping. Control MAC values, expressed as mean +/- standard deviation, were 1.31 +/- 0.1% for HAL and 1.46 +/- 0.05% for ISO. DEX reduced HAL MAC from 1.31 +/- 0.1% to 0.36 +/- 0.22% (72 +/- 17% MAC reduction) and ISO MAC from 1.46 +/- 0.05% to 0.83 +/- 0.2% (43 +/- 14% MAC reduction). Heart rate (HR) was decreased in both DEX groups at 1 MAC, with no differences between HAL and ISO. The mean arterial pressure was significantly depressed in the DEX + ISO group compared with the ISO only group. This difference in mean arterial blood pressure (MABP) was not seen between the DEX + HAL and HAL only groups. Respiratory depression was minor at 1 MAC with both inhalant anaesthetics. DEX reduced the MAC of HAL to a degree greater than it decreased the MAC of ISO. The effects of DEX on HR and ventilation were similar in rats anaesthetized with HAL or ISO at 1 MAC; however, hypotension was more pronounced when DEX was combined with ISO at 1 MAC.

Adrenergic alpha-Agonists↗