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The effect of intravenous infusion of prostaglandin E1 on cutaneous microcirculation in black foot disease.

In order to evaluate the effect of an intravenous infusion of prostaglandin E1 (PGE1), 80 micrograms/day for two weeks, on microcirculatory vasculature in seven patients (M:F = 3:4, age 60-78) with black foot disease (a peripheral vascular disease of undefined etiology), we applied laser Doppler velocimetry to measure the maximal cutaneous microcirculatory flow (LDF) at a proximal site near gangrenous ulcers of the foot. Maximal flow was induced by local warming to 42 degrees C with a modified laser Doppler heating probe. Three phasic measurements were recorded, i.e., during pretreatment, treatment and follow-up with the separation interval being two weeks. The net maximal LDF (LDF at 42 degrees C minus LDF at room temperature) increased from 8.8 +/- 4.0 to 11.9 +/- 4.0 volt, p < 0.05. Cutaneous vascular conductance (CVC) was calculated as LDF/mean BP. Mean BP showed no significant change before or after treatment. Net CVC was changed from 7.5 +/- 3.1 to 11.9 +/- 4.0 volt/100 mmHg, p < 0.05. The LDF dropped significantly during the two-week period between treatment and follow-up in five subjects (10.8 +/- 3.4 vs 4.6 +/- 1.8, p < 0.05), while the follow-up LDF was close to the control data (4.6 +/- 1.8 vs 6.3 +/- 2.2, p = NS). Hence, we conclude that PGE1 may beneficially enhance microcirculatory blood flow in black foot disease through direct vasodilatory effects.

Aged↗

Pharmacokinetics of platinum in cancer patients following intravenous infusion of cis-diammine(glycolato)platinum, 254-S.

The pharmacokinetics of platinum in cancer patients were examined following an intravenous infusion of cis-diammine(glycolato) platinum, 254-S. The plasma concentrations of total platinum, which decreased biexponentially after the infusion, were proportional to the dose over the range of 10 to 120 mg/m2, suggesting linearity of the pharmacokinetics. The plasma concentrations of ultrafilterable platinum were similar to those of total platinum and there was little difference in the pharmacokinetic parameters between total platinum and ultrafilterable platinum. These findings show that almost all of the platinum derivative is unbound, which is thought to be the active form, in plasma after administration of 254-S. Platinum was eliminated from blood faster when given as 254-S rather than as cisplatin because of the low protein binding. The urinary recovery within 24 hours was about half of the dose, suggesting that platinum given as 254-S was distributed to various tissues and organs in an active form.

Adolescent↗

Stimulation of human prolactin secretion by intravenous infusion of L-tryptophan.

Previous studies have demonstrated that the secretion of human prolactin is regulated primarily by factors that influence catecholamines of the hypothalamus. In an effort to identify other factors that may regulate prolactin secretion, the amino acid L-tryptophan, a precursor in the synthesis of serotonin, was infused into normal human volunteers. Intravenous infusion of L-tryptophan, 5-10 g over a 20 min period, but not equivalent amounts of 17 other amino acids, induced marked increases in serum prolactin concentrations in eight normal human volunteers. Increases of 20-200 ng/ml above the control level were observed with peak values at 20-45 min after initiation of the infusion. In addition, infusion of L-tryptophan was associated with decreases in serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyrotropin in those subjects in whom the base-line serum hormone concentration was above the lower limits of assay detectability. No consistent change was observed in serum concentrations of growth hormone, cortisol, or glucose. Four subjects with juvenile diabetes demonstrated increases in serum prolactin values comparable with those observed in healthy individuals in response to infusions of L-tryptophan. Serum prolactin values in patients with surgically induced hypopituitarism were undetectable or deficient after infusion of 10 g of L-tryptophan. In this respect, infusion of L-tryptophan was equally effective in these subjects as the standard chlorpromazine stimulation test in identifying patients with hypopituitarism, indicating that the infusion of L-tryptophan may serve as a sensitive and reliable clinical test of prolactin secretory reserve. Further studies relating to the possible mechanism of action of L-tryptophan indicated that infusion of 5-hydroxytryptophan represents a much more potent stimulus for the secretion of prolactin and that premedication with the serotonin antagonist, methysergide maleate, serves to blunt the effect of L-tryptophan on prolactin secretion. These results support the concept that the effect of L-tryptophan on the secretion of human prolactin is mediated through its conversion to serotonin and are consistent with reported experimental observations that serotonin may participate in the reciprocal regulation of prolactin and gonadotropins.

5-Hydroxytryptophan↗

Echocardiographic monitoring of left ventricular regional motion during hyperventilation and intravenous infusion of trometamol (tris) for detection of variant angina.

BACKGROUND: In spite of constant progress and development of new diagnostic tests, the detection of variant angina, which occurs in approximately 30% of patients with ischaemic heart disease (IHD), remains challenging. AIM: To assess the sensitivity and specificity of echocardiographically monitored transient abnormalities of regional wall motion of left ventricle (LV) during hyperventilation after intravenous infusion of trometamol (TRIS-buffer) for the detection of coronary artery spasm. METHODS: The study group consisted of 72 patients (14 women and 58 men, aged from 32 to 69 years) with IHD. A control group was composed of 20 healthy men. Patients with IHD were divided into two groups. Group I consisted of 46 patients with Prinzmetal's angina whereas group II was composed of 26 patients with exertional angina and a history of myocardial infarction. Two-dimensional echocardiographic monitoring of LV contractility was carried out during hyperventilation after an intravenous infusion of 100 ml of trometamol. RESULTS: Transient abnormalities of regional LV wall motion during infusion of trometamol and hyperventilation occurred in 91% of patients from group I and in 8% of patients from group II (p<0.00001). Electrocardiographic ST-segment changes during hyperventilation-trometamol test were observed in 63% of patients from group I and in 23% of patients from group II (p<0.0001). No transient regional dyssynergy of LV nor ST-segment changes during hyperventilation-trometamol test in the control group were observed. The sensitivity and specificity of regional LV wall motion during hyperventilation-trometamol test in the identification of patients with variant angina were 91% and 92%, respectively, and the sensitivity and specificity of ST-segment changes - 63% and 76%, respectively. CONCLUSIONS: Echocardiographic monitoring of regional LV wall motion during hyperventilation after intravenous infusion of trometamol is a sensitive and specific test for detection of variant angina.

Adult↗

Stepwise intravenous infusion of apomorphine to determine the therapeutic window in patients with Parkinson's disease.

A new experimental strategy was applied to determine the concentration-effect relation and the therapeutic window of apomorphine in individual patients with Parkinson's disease. Apomorphine was administered by a stepwise intravenous infusion. The infusion rate was increased by 10 micrograms/kg/h every 20 minutes, up to 100 micrograms/kg/h or less when adverse effects occurred. Thereafter, the infusion rate was decreased in a stepwise fashion until zero. Plasma apomorphine concentrations were measured every 20 minutes. Clinical efficacy (tapping score and tremor), dyskinesia, and adverse effects were monitored at the same time. The mean clearance of apomorphine was 4.5 L/min (2.2 to 6.6 L/min). Of the 10 patients, 8 responded to apomorphine. The effects were quantal rather than continuous. Within each patient, the concentrations at onset and offset of effect generally were similar. Significant interpatient variability was observed with respect to minimal concentration for each of the effects. Clinical efficacy occurred at a mean minimal effective concentration (MEC) of 4.7 ng/mL (range 1.4 to 10.7 ng/mL). Dyskinesia was observed at a mean concentration of 8.5 ng/mL (range 2.7 to 20 ng/mL). This value was not significantly different from the MEC. The mean minimal toxic concentration was 16.7 ng/mL (8.5 to 24.5 ng/mL) and was significantly different from the mean MEC. In conclusion, the stepwise increase and decrease of the intravenous infusion rate is a suitable tool for the establishment of the concentration-effect relation of apomorphine in individual patients. The finding of a narrow therapeutic window, in which the onset concentrations vary from patient to patient, underlines the need for accurate and individualized dosing.

Adult↗

Surveillance of adverse reactions in patients self-infusing intravenous immunoglobulin at home.

This is the first prospective study of adverse reactions occurring in primary-antibody-deficient patients self-infusing intravenous immunoglobulin at home. One hundred nineteen patients, already self-infusing at home, were entered into the study. They had been fully instructed about all aspects of adverse reactions, including their prevention and treatment. In the event of any adverse reaction, a form was completed detailing the product, the dose, the symptoms that occurred and the time they lasted, the rate of infusion, and other relative information such as predisposing factors and any medication taken. The severity of reactions were classified as mild, moderate, or severe. The total number of reactions documented was 19 in 2031 infusions, and all resolved without medical aid. No serious reactions occurred. Excluding those reactions in which predisposing factors were identified, the overall reaction rate was 0.7%. In conclusion the study showed the reaction rate in patients self-infusing intravenous immunoglobulin at home was low following formal training of selected patients at recognized training centers.

Adolescent↗

Intravenous infusion anesthesia with Propofol-Midazolam-fentanyl for experimental surgery in swine.

There is a need for prolonged anesthesia procedures in experimental surgery. Animals in this study received fentanyl, Midazolam, and Propofol administered by continuous intravenous infusion for anesthesia along with controlled ventilation. Time of anesthesia was 413 +/- 95 min. Animals could be extubated 20 +/- 12 min after operation. Animals recovered completely from anesthesia by day 1 after surgery with almost normal physical activity. This study clearly shows that intravenous infusion anesthesia is safe and easy to handle in prolonged anesthesia for experimental surgery in swine. This anesthetic protocol can also be used for intraoperative transportation.

Abdomen↗

In vivo determinations of labelling index of metastatic colorectal carcinoma and normal colonic mucosa using intravenous infusions of bromodeoxyuridine.

In vivo determination of the labelling index of metastatic colon carcinoma was performed in 14 patients following intravenous infusion of bromodeoxyuridine (BrdU), at doses of 100 and 50 mg/M2. No toxicity was seen. Labelled cells were detected by an immunohistochemical technique using a monoclonal antibody to BrdU. Labelling was uniform and highly specific with good preservation of morphology. Labelling index values ranged from 15.0-40.6% for metastatic lesions and 3.6%-20% for normal colonic mucosa, with mean values of 24% and 11%, respectively. This represents a useful new method for in vivo labelling index determination in solid tumors.

Bromodeoxyuridine↗

Effects of intravenously infused pituitary adenylate cyclase-activating polypeptide on adenohypophyseal Hormone secretion in normal men.

The possible stimulatory effects of an intravenous infusion of increasing amounts of pituitary adenylate cyclase-activating polypeptide (PACAP) on anterior pituitary hormone secretions were evaluated in humans. Successively increasing doses of PACAP-38 (2, 4 and 8 pmol.kg-1.min-1; each dose for 20 min) were infused i.v. in 7 normal male subjects. On a different occasion, the same subjects were tested with vasoactive intestinal peptide (VIP; 4 pmol.kg-1.min-1 for 60 min). Circulating GH, ACTH, PRL, TSH and gonadotropin concentrations were measured before PACAP infusion and every 20 min, just before increasing the infusion dose of PACAP. Blood samples were taken before and every 15 min after the beginning of VIP administration. Serum levels of GH, TSH and gonadotropins did not change during PACAP or VIP infusion. Circulating ACTH and PRL concentrations were not modified by the infusion of the lowest dose of PACAP, whereas they were significantly increased in a dose-response fashion when higher amounts of PACAP were given. PRL, but not ACTH levels were significantly increased by VIP infusion. These data show for the first time in humans that ACTH and PRL secretions from the anterior pituitary gland are stimulated by the systemic administration of PACAP. In addition, since VIP stimulated only PRL secretion, PACAP-induced ACTH release appears to be mediated by specific receptors.

Adult↗

Increased secretion of adrenal progesterone explains the lack of response of oviductal embryo transport to a short intravenous infusion of estradiol in the rat.

Administration of estradiol (E2) as a single subcutaneous injection, but not as a short intravenous infusion (less than 150 min), accelerates oviductal embryo transport in pregnant rats although the first mode determines lower E2 circulating levels. Since progesterone (P) can antagonize the effect of E2 on embryo transport we examined the circulating P levels under these two modes of E2 administration. Rats were treated on day 1 of pregnancy with 5 micrograms E2 given s.c. or i.v. (10 min infusion). Other groups were either hypophysectomized (HPX), adrenalectomized (ADX) or ovariectomized (OVX) prior to E2 treatment to prevent P rise, or were treated with E2 plus RU486 to block the action of P. Some groups were autopsied at short intervals following treatment to measure P levels and others 24 h later to assess the effect of treatments on embryo transport. P was increased several fold by i.v. infusions of E2 or vehicle alone in intact and OVX rats but not in HPX or ADX rats, whereas s.c. administration of E2 did not change P levels unless it was given concomitantly with i.v. infusion of vehicle. The short i.v. infusion of E2 accelerated embryo transport in HPX, ADX, or RU486 treated rats but not in intact rats. The s.c. injection of E2 accelerated embryo transport even when it was accompanied by an i.v. infusion of vehicle. The data does not exclude the participation of glucocorticoids in the above phenomena but agrees with the view that it is the transient increase in adrenal P secretion which blunts the oviductal response to a brief pulse of E2.

Adrenalectomy↗

Intravenous infusion pharmacokinetics of desferrioxamine in thalassaemic patients.

Pharmacokinetic investigation of desferrioxamine (DFO) was conducted in 11 thalassaemic patients following continuous intravenous infusion of 50 mg/kg/24 hr over 48 hr. Serial venous blood samples were obtained at regular time intervals during and on stopping DFO infusion. Plasma samples were processed with the addition of radioactive iron (59Fe) to stabilize free ligand forms of DFO and its metabolites. This resulted in the formation of both radioactive and nonradioactive forms of ferrioxamine and its metabolites. Following solid-phase extraction, plasma samples were analyzed by a reversed-phase HPLC and monitored by simultaneous UV-visible radioactive detection. DFO was found to be eliminated from the blood in a biexponential manner with a systemic clearance of 0.50 +/- 0.24 liters/hr/kg. The terminal half-life was 3.05 +/- 1.30 hr, and the volume of distribution was 1.88 +/- 1.0 liters/kg at the terminal phase and 1.35 +/- 0.65 liters/kg at steady state. The AUC of DFO was 354 +/- 131 mumol/liter.hr. The major metabolite of DFO, DFO-metabolite B, has an initial half-life of 1.33 +/- 0.61 hr and is usually present at lower concentrations relative to the parent compound with an AUC of 191 +/- 106 mumol/liter.hr.

Chromatography, High Pressure Liquid↗

Penetration of trovafloxacin into cerebrospinal fluid in humans following intravenous infusion of alatrofloxacin.

A single-dose study was conducted to determine concentrations of trovafloxacin (CP-99,219) achieved in the cerebrospinal fluid (CSF) relative to those in the serum of healthy subjects after intravenous infusion of alatrofloxacin (CP-116,517), the alanyl-alanyl prodrug of trovafloxacin. Twelve healthy subjects were administered single doses of alatrofloxacin at a trovafloxacin equivalent of 300 mg as an intravenous infusion over 1.0 h. CSF samples were taken by lumbar puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the infusion; each subject was sampled at only one time point. Serum samples were taken from each subject at the time of CSF collection. A mean concentration of 5.8 microg of trovafloxacin per ml was present in serum 1.0 h after the start of the infusion. CSF/serum ratios ranged from 0.14 to 0.33 in the postdistribution phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common adverse events were dizziness, nausea, and rash and were mild or moderate in intensity. The potency of trovafloxacin against susceptible organisms, coupled with its rapid penetration of CSF following the intravenous administration of alatrofloxacin, suggests that it may be useful in the treatment of bacterial meningitis in humans.

Adolescent↗

[Clinical study on the effect of 24-hour continuous intravenous infusion of CDDP in far-advanced and recurrent carcinoma of the gastrointestinal tract].

This clinical study was undertaken in order to evaluate the effect of CDDP on 43 patients with far-advanced or recurrent carcinoma of the gastrointestinal tract. For all these patients, CDDP at 100 mg/m2 had been administered by continuous intravenous infusion for 24 hours and repeated one to seven times at an interval of 3 to 4 weeks. The effect of this therapy was assessed according to the criteria of clinical evaluation of chemotherapy for solid cancers by Koyama and Saito. The response rate for both complete and partial response was 27.9% among all 43 patients, including 47.1% (8/17) for gastric cancer, 33.3% (1/3) for esophageal cancer, 25.0% (1/4) for hepatocellular carcinoma, 25.0% (1/4) for carcinoma of the gallbladder or bile duct, 20.0% (1/5) for pancreatic cancer and none (0/10) for colorectal cancer. In particular, a good response rate of 37.5% (3/8) was obtained for patients with recurrent tumor and one of 33.3% (6/18) for those with palliative resection of the primary tumor, which was much higher that the rate of 17.6% (3/17) for those without resection. As for the side effects of CDDP therapy, gastrointestinal symptoms were most frequently found in 78.3% of patients followed by bone marrow suppression in 15.2%, and abnormalities of hepatic and renal function in 4.3% and 4.3%, respectively. Consequently, 24-hour continuous intravenous infusion of CDDP was considered to be effective for far-advanced or recurrent carcinoma, especially in cases of gastric cancer.

Carcinoma, Hepatocellular↗

Optimal timing of neutron irradiation for boron neutron capture therapy after intravenous infusion of sodium borocaptate in patients with glioblastoma.

PURPOSE: A cooperative study in Europe and Japan was conducted to determine the pharmacokinetics and boron uptake of sodium borocaptate (BSH: Na(2)B(12)H(11)SH), which has been introduced clinically as a boron carrier for boron neutron capture therapy in patients with glioblastoma. METHODS AND MATERIALS: Data from 56 patients with glioblastoma who received BSH intravenous infusion were retrospectively reviewed. The pharmacokinetics were evaluated in 50 patients, and boron uptake was investigated in 47 patients. Patients received BSH doses between 12 and 100 mg/kg of body weight. For the evaluation, the infused boron dose was scaled linearly to 100 mg/kg BSH. RESULTS: In BSH pharmacokinetics, the average value for total body clearance, distribution volume of steady state, and mean residence time was 3.6 +/- 1.5 L/h, 223.3 +/- 160.7 L, and 68.0 +/- 52.5 h, respectively. The average values of the boron concentration in tumor adjusted to 100 mg/kg BSH, the boron concentration in blood adjusted to 100 mg/kg BSH, and the tumor/blood boron concentration ratio were 37.1 +/- 35.8 ppm, 35.2 +/- 41.8 ppm, and 1.53 +/- 1.43, respectively. A good correlation was found between the logarithmic value of T(adj) and the interval from BSH infusion to tumor tissue sampling. About 12-19 h after infusion, the actual values for T(adj) and tumor/blood boron concentration ratio were 46.2 +/- 36.0 ppm and 1.70 +/- 1.06, respectively. The dose ratio between tumor and healthy tissue peaked in the same interval. CONCLUSION: For boron neutron capture therapy using BSH administered by intravenous infusion, this work confirms that neutron irradiation is optimal around 12-19 h after the infusion is started.

Adult↗

Failure of intravenous infusions from extravasation and phlebitis.

A survey was done to compare the rates at which phlebitis and extravasation cause failure of intravenous infusions lasting more than 24 hours. Slightly more infusions failed due to phlebitis than to extravasation but extravasation did not occur earlier or later than phlebitis or differ significantly from it in frequency when different types of infusions were compared. Univariate life table analysis indicated that the co-infusion of blood, potassium or cephalosporin antibiotics slightly increased and that higher flow rates markedly increased failure, that infusions including continuous heparin and steroids had markedly decreased failure, and that failure was not significantly affected by other antibiotics or by differences in sex, age, location of infusion site or time of year. Multivariate analysis showed that the above differences were statistically significant only for infusion rate, heparin and steroids.

Adult↗

Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors.

PURPOSE: To evaluate the feasibility of administering irinotecan as a continuous intravenous infusion for 14 to 21 days. PATIENTS AND METHODS: Patients with solid tumors refractory to standard therapy received continuous infusions of irinotecan by means of an ambulatory infusion pump. The starting dosage was 12.5 mg/m(2)/d for 14 days every 3 weeks. After identification of the maximum-tolerated dose for the 14-day infusion schedule, the protocol was amended to prolong the infusion duration to 17 and 21 days. Pharmacokinetics of irinotecan and SN-38 and its glucuronide were determined using high-performance liquid chromatography and noncompartmental modeling. RESULTS: Thirty-three patients received 85+ courses. At the first dose level (12.5 mg/m(2)/d), cumulative grade 3 or 4 diarrhea and grade 3 or 4 neutropenia occurred in three of five patients. At a dosage of 10 mg/m(2)/d, 14-day administration resulted in grade 4 diarrhea in two of six patients and one episode of grade 4 vomiting occurred, whereas with 17-day administration, one episode of grade 3 nausea and two episodes of grade 3 or 4 diarrhea were observed in six patients. Increasing the number of days of infusion to 21 days was not feasible because of cumulative diarrhea. Hematologic toxicity was rare. The mean metabolic SN-38 area under the curve/irinotecan area under the curve ratio was 16% +/- 6% compared with 3% to 5% after short infusion schedules involving therapeutic dosages. Partial responses were observed in two patients with extraovarian and colorectal cancer. CONCLUSION: The recommended dosage is 10 mg/m(2)/d for 14 days, repeated every 3 weeks. Enhanced metabolism of irinotecan to SN-38 may explain in part the low recommended dose for this schedule.

Adult↗

24-hour intravenous infusion via the marginal ear vein in the New Zealand white rabbit.

A method was needed to conduct a 24-h intravenous infusion procedure in rabbits that minimized animal restraint and allowed unlimited access to the animal by research staff. We catheterized 16 male and 16 female New Zealand White rabbits (Oryctolagus cuniculus) by inserting an indwelling human infant catheter into the marginal ear vein. The catheter was connected, via an extension set, to a small, lightweight, ambulatory pump with predetermined pump rates; the pump was placed in a Lycra jacket that the rabbit was wearing. Toxicokinetic samples, electrocardiograms, and clinical pathology samples were collected at multiple time points. Pump accuracy was verified by collecting the pre- and post-dose weights of the pumps as well as infusion start and stop times. Depending on the infusion rate, pumps were changed every 5 or 10 h or at the end of 24 h. The accuracy of these pumps was between 5% and 10% of the calculated target volume from 0 to 20 h. The lack of need for surgery or long-term restraint and tethering is a refinement in infusion technology and animal use.

Animals↗

Lansoprazole regimens that sustain intragastric pH > 6.0: an evaluation of intermittent oral and continuous intravenous infusion dosages.

BACKGROUND: Orally and intravenously administered proton pump inhibitors have been shown to reduce rebleeding rates, surgery and transfusion requirement. AIM: To compare lansoprazole intravenous and orally disintegrating tablet (Prevacid SoluTab) regimens with a pantoprazole intravenously administered regimen in sustaining intragastric pH >6.0. METHODS: Two similarly designed three-way, randomized crossover studies each enrolled 36 Helicobacter pylori-negative healthy volunteers. Study 1 regimens included intravenously administered bolus followed by 24-h continuous infusion (lansoprazole 90 mg, 6 mg/h; lansoprazole 120 mg, 6 mg/h; pantoprazole 80 mg, 8 mg/h). Study 2 regimens included intravenous bolus followed by lansoprazole orally disintegrating tablet or intravenous continuous infusion for 24 h (lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg every 6 h; lansoprazole 120 mg, 9 mg/h; pantoprazole 80 mg, 8 mg/h). Percentage of time pH >6.0 was assessed with 24-h intragastric pH monitoring. RESULTS: All regimens produced comparable gastric acid suppression. In both studies, regimens superior to pantoprazole included lansoprazole 90 mg, 6-mg/h; lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg q.d.s. and lansoprazole 120 mg, 9 mg/h (P < or = 0.013). The lansoprazole 120-mg, 6-mg/h regimen (P = 0.082) was not superior to pantoprazole in percentage of time intragastric pH >6.0. Mild reaction at the intravenous injection site was the most frequently reported adverse event. CONCLUSIONS: The intravenous bolus and continuously infused lansoprazole or intravenous bolus and intermittent lansoprazole orally disintegrating tablet regimens are as effective as intravenous pantoprazole in sustaining intragastric pH >6.0.

2-Pyridinylmethylsulfinylbenzimidazoles↗