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Results for “Administration, Intravenous”

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PubMed2003

The renal effects of minimally nephrotoxic doses of ibandronate and zoledronate following single and intermittent intravenous administration in rats.

Rapid, intravenous (i.v.) administration of high doses of bisphosphonates has been associated with acute renal toxicity. This controlled, preclinical study over 25 weeks investigated the potential for subclinical renal damage to accumulate to clinically relevant levels when minimally nephrotoxic doses of ibandronate (1 mg/kg) or zoledronate (1 or 3 mg/kg) were given intermittently, with a between-dose interval of 3 weeks, or as a single dose by i.v. injection. In rats, a single dose and intermittent dosing of ibandronate resulted in a similar incidence (one of six and two of six rats, respectively) and severity score (1.0 for both) of proximal tubular degeneration and single cell necrosis. No accumulation of histopathological renal damage occurred. However, intermittent dosing of zoledronate induced a higher incidence (six of six rats) and severity score (3.0) of renal damage compared with single dosing (four of six rats and 1.3, respectively). Accumulation of renal damage was also observed for a lower intermittent dose of zoledronate (1 mg/kg) that had not exhibited histopathological renal damage when given as a single 1 mg/kg dose. Biochemical parameters confirmed these histopathological findings. In summary, the results from this study indicate that administering ibandronate intermittently provides sufficient time for regeneration of potential subclinical renal damage.

Acetylglucosamine↗

PubMed1978

Comparison of intraduodenal and intravenous administration of amino acids on gastric secretion in healthy subjects and patients with duodenal ulcer.

The ability of an amino acid mixture given intraduodenally or intravenously to stimulate gastric secretion is compared in healthy subjects and in duodenal ulcer patients. Graded amounts of amino acids by both routes produced a similar increase in acid output in healthy subjects, reaching about 30% of the maximal response to pentagastrin. Serum gastrin concentrations remained virtually unchanged but serum alpha amino acid nitrogen levels were about twice as high with intravenous as with intraduodenal administration. Intravenously administered amino acids produced a significantly higher acid output in patients with duodenal ulcer than in healthy subjects, but did not produce a significant increase in gastric acid or pepsin secretion when combined with a pentagastrin infusion as compared with pentagastrin alone. Cimetidine (2 mg/kg/h) added to intravenous amino acid infusions caused almost complete suppression of acid secretion. This study indicates that amino acids are capable of stimulating gastric secretion after intraduodenal and after intravenous administration. The response to the latter is significantly higher in patients with duodenal ulcer than in healthy subjects, does not appear to involve gastrin release, is not affected by pentagastrin, and is strongly suppressed by histamine H2-blocker.

Adult↗

PubMed1997

Pharmacokinetics of adriamycin and adriamycinol after intravenous administration of adriamycin to rats with water-deprivation for 48 hours.

Because hormonal, physiological, and biochemical changes occurring in dehydrated patients could alter the pharmacokinetics of the drugs used to treat the patients, the pharmacokinetics and tissue distribution of adriamycin (ADM) and adriamycinol were investigated after 1-min intravenous administration of ADM (16 mg kg-1) to control and 48-h water-deprived rats. After intravenous administration of ADM, the plasma levels of ADM were considerably higher from 3 h in water-deprived rats (n = 10) than those in control rats (n = 11). The total body clearance was significantly slower (80.3 compared with 110 mL min-1 kg-1) in water deprived rats than that in control rats. Adriamycinol was detected in plasma up to 30 min for water-deprived rats, but it was detected only up to 5 min for control rats with considerably higher levels in water-deprived rats. The amount of ADM obtained from kidney, liver, spleen, and small intestine was significantly higher in water-deprived rats (n = 6) than those in control rats (n = 5). The amount of adriamycinol obtained from liver was significantly higher in water-deprived rats. All 11 control rats survived over 48 h whereas 5 water-deprived rats died within 8 h after intravenous administration of ADM, suggesting that the intravenous dose of ADM in water-deprived patients may need modification if the present rat data could be extrapolated to humans.

Animals↗

PubMedDate not supplied

Gene delivery to the rat liver using cationic lipid emulsion/DNA complex: comparison between intra-arterial, intraportal and intravenous administration.

OBJECTIVE: To compare the efficiency of intra-arterial, intraportal, and intravenous administration of cationic lipid emulsion/DNA complex, as used for gene transfer to rat liver. MATERIALS AND METHODS: DNA-carrier complex for the in-vivo experiment was prepared by mixing DNA and a cationic lipid emulsion. According to the administration route used (intra-arterial, intraportal, or intravenous), the animals were assigned to one of three groups. The heart, lung, liver, spleen and kidneys were removed and assayed for total protein and luciferase concentration. RESULTS: The cationic lipid emulsion/DNA complex used successfully transfected the various organs via the different administration routes employed. Luciferase activity in each organ of untreated animals was negligible. Liver luciferase values were significantly higher in the groups in which intra-arterial or intraportal administration was used. CONCLUSION: The intra-arterial or intraportal administration of cationic lipid emulsion/DNA complex is superior to intravenous administration and allows selective gene transfer to the liver.

Animals↗

PubMed1996

CV6209 inhibits airway wall thickening and airway hyperresponsiveness to histamine induced by intravenous administration of platelet-activating factor in guinea pigs.

We studied the effect of intravenous administration of platelet-activating factor (PAF) on airway responsiveness to histamine and airway wall thickening in guinea pigs. Guinea pigs were killed and the lungs were fixed in formalin. Slides from paraffin-embedded sections of the lungs were stained and the airways that were cut in transverse section were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyzer and we calculated two indices, an index of airway wall thickening and one of airway hyperresponsiveness to histamine, from changes of baseline-Raw and peak-Raw following intravenous administration of histamine before and after PAF administration. The infusion of 600 ng/kg PAF for 1 h induced an increase in the thickness of the airway wall in main bronchi demonstrable by histological examination. In analysis of airway function, the infusion of 600 ng/kg PAF for 1 h induced airway hyperresponsiveness to histamine with airway wall thickening. The PAF antagonist CV6209, which was given intravenously 30 min prior to PAF administration, inhibited these effects of PAF in a dose-dependent manner, suggesting PAF may induce airway wall thickening and airway hyperresponsiveness through PAF receptors in the airways.

Airway Resistance↗

PubMed1995

Pharmacokinetics of trimethoprim/sulphachlorpyridazine in horses after oral, nasogastric and intravenous administration.

In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half-lives, clearance, bioavailability, volume of distribution) were determined both for TMP and SCP. Following intravenous administration, the volume of distribution at steady-state (Vd(ss)) was significantly larger for TMP (1.51 +/- 0.25 L/kg than for SCP (0.26 +/- 0.05 L/kg. The clearance was 7.73 +/- 2.26 mL/min.kg for TMP and 2.64 +/- 0.48 mL/min.kg for SCP. For both TMP and SCP, mean peak plasma concentrations (Cmax) and the bioavailabilities (F) were reduced significantly when the drugs were mixed with concentrate (ct) as compared with those after nasogastric administration (ngt) (Fct = 44.3 +/- 10.7% vs. Fngt = 68.3 +/- 12.5% for TMP; Fct = 46.3 +/- 8.9% vs. Fngt = 67.3 +/- 13.7% for SCP). Following the administration of TMP and SCP mixed with concentrate, the plasma concentration-time curves showed a biphasic absorption pattern in all horses. The first peak occurred 1-2 h and the second peak 8-10 h after administration of the combination preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1964

INTERFERON-LIKE VIRAL INHIBITOR IN RABBITS AFTER INTRAVENOUS ADMINISTRATION OF ENDOTOXIN.

Intravenous injection into rabbits of endotoxin or killed cells of Escherichia coli induced, in 1 hour, a viral inhibitor detectable in serum. The inhibitor disappeared from the serum in 7 to 24 hours, and was only active after incubation with rabbit cell cultures. Like interferon, it did not preferentially inactivate virus directly, was ineffective in chick cells, was inactivated by trypsin, and was not sedimentable. Unlike interferon, the inhibitor was heat labile. Nucleic acid or nucleotides apparently play no role in its induction.

Animals↗

PubMed1985

[Comparison of the results of ethacizin pharmacodynamics and pharmacokinetics in a single intravenous administration].

A single intravenous injection of 30-50 mg ethacizin produces a favourable antiarrhythmic effect in 80-85% of patients with ventricular disorders of cardiac rhythm. The drug's action already begins "on the needle", reaches its peak within 3-5 minutes and lasts for 1-2 hours. A two-compartment model adequately represents ethacizin pharmacokinetics. The average ethacizin half-distribution and half-elimination periods are 4.7 and 154.4 minutes, respectively, and its clearance rate is 0.99 1/min. Therapeutic plasma concentration of the drug varies between 30-50 and 300-400 ng/ml.

Adolescent↗

PubMed1997

Factors controlling the efficiency of cationic lipid-mediated transfection in vivo via intravenous administration.

The factors controlling the transfection efficiency of cationic lipid carrier systems following intravenous administration are poorly understood. Using N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) combined with Tween 80 as a carrier system and cDNA of luciferase or beta-galactosidase gene as a reporter, we investigated the importance of DOTMA to DNA ratio and the ratio of DOTMA to Tween 80 in the lipid formulation in determining the site and level of transgene expression following intravenous administration. The data show that all of the internal organs, including lung, liver, spleen, heart and kidneys, expressed the transgene upon systemic administration into animals with 25 micrograms of plasmid DNA when complexed with DOTMA-Tween 80 lipid formulation. The transfection efficiency was dependent on both DOTMA to DNA, and DOTMA to Tween 80 ratios. Among the organs examined, the lung appeared to be more transfectable than other organs. A better transfection activity was obtained with higher DOTMA to DNA and DOTMA to Tween 80 ratios. Time-response curve shows that gene expression was transient with a maximal level between 10 and 24 h after injection. Results from tissue distribution studies with 125I-labeled plasmid DNA and Southern analysis suggest that the transient expression is the result of the loss of transgene from the transfected cells. These results suggest that cationic lipid-based delivery systems can be efficient for gene delivery if the composition of the DNA-lipid complexes is properly controlled.

Animals↗

PubMed2005

Continuous versus intermittent intravenous administration of antibacterials with time-dependent action: a systematic review of pharmacokinetic and pharmacodynamic parameters.

We performed a systematic review of randomised clinical trials to evaluate the comparative pharmacokinetic and pharmacodynamic properties of the continuous versus intermittent mode of intravenous administration of various antibacterials. Data were identified from PubMed (January 1950 to January 2005), Current Contents, the Cochrane central register of controlled trials, and references from relevant articles and reviews. Seventeen randomised clinical trials comparing continuous with intermittent intravenous administration of the same antibacterial regimen and examining the pharmacokinetic and pharmacodynamic properties were included in this systematic review. We reviewed data regarding the clinical setting, number of participants, antibacterial agents and dosages used, as well as maximum serum concentration (Cmax), trough serum concentration (Cmin), steady-state or plateau serum concentration (Css), area under the concentration-time curve (AUC), time above the minimum inhibitory concentration (MIC) [T>MIC], AUC: MIC, elimination rate constant, elimination half-life, volume of distribution and systematic clearance. The mean Cmax of the intermittently administered antibacterials was higher compared with Css achieved by the continuous infusion of the same antibacterial in all eligible studies (Cmax was on average 5.5 times higher than Css, range 1.9-11.2). Css was on average 5.8 times higher than the Cmin of the intermittently administered antibacterials (range 1.2-15.6). In three of six studies the length of time that the drug concentration was above the MIC of the responsible pathogens was longer in patients receiving the antibacterials continuously. In conclusion, the reviewed data suggest that the continuous intravenous infusion of antibacterials with time-dependent bacterial killing seems to be superior than the intermittent intravenous administration, from a pharmacodynamic point of view, at least when treating bacteria with high MIC values for the studied antibacterials.

Animals↗

PubMed2002

Blood-brain barrier drug targeting enables neuroprotection in brain ischemia following delayed intravenous administration of neurotrophins.

The blood-brain barrier (BBB) is the rate-limiting step in the translation of neurotrophin neuroscience into clinically effective neurotherapeutics. Since neurotrophins do not cross the BBB, these proteins cannot be used for neuroprotection following intravenous administration, and it is not feasible to administer these molecules by intra-cerebral injection in human stroke. The present studies describe the development of the chimeric peptide brain drug targeting technology and the use of brain-derived neurotrophic factor (BDNF) chimeric peptides in either global or regional brain ischemia. The BDNF chimeric peptide is formed by conjugation of BDNF to a monoclonal antibody (MAb) to the BBB transferrin receptor, and the MAb acts as a molecular Trojan Horse to ferry the BDNF across the BBB via transport on the endogenous BBB transferrin receptor. High degrees of neuroprotection in transient forebrain ischemia, permanent middle cerebral artery occlusion, or reversible middle cerebral artery occlusion are achieved with the delayed intravenous administration of BDNF chimeric peptides. In contrast, no neuroprotection is observed following the intravenous administration of unconjugated BDNF, because the neurotrophin does not cross the BBB in vivo.

Animals↗

PubMed1997

Prophylactic intravenous administration of caffeine and recovery after ambulatory surgical procedures.

OBJECTIVE: To determine whether prophylactic intravenous administration of caffeine, to daily caffeine users, decreases the frequency of postoperative headache and shortens recovery time. DESIGN: The study was a prospective, randomized, double-blind investigation with predetermined sample size and statistical power. MATERIAL AND METHODS: After Mayo Institutional Review Board approval and informed consent were obtained, 300 adult ambulatory surgical patients were enrolled in this study, which included randomization to receive either placebo or caffeine (200 mg intravenously) in the postanesthesia care unit. While recuperating, patients were allowed their choice of postoperative beverages. Before dismissal, patients completed a questionnaire providing details about intake of caffeine and tobacco, history of headache, and demographic data. Patients were considered "at risk" for symptoms of caffeine withdrawal if they did not drink a caffeinated beverage after the surgical procedure. RESULTS: Completed questionnaires were obtained from 234 patients. Patients at risk for symptoms of caffeine withdrawal were less likely to have a postoperative headache if they received caffeine intravenously rather than placebo-10% versus 23% (P < 0.05). Time until recovery was not significantly different between caffeine and placebo study groups. CONCLUSION: We conclude that prophylactic intravenous administration of caffeine was beneficial for those patients at risk for symptoms of caffeine withdrawal. For patients who consume caffeinated beverages on a daily basis, we recommend prophylactic administration of caffeine on the day of an ambulatory surgical procedure and anesthesia.

Adolescent↗

PubMed1989

[Experimental studies on drug uptake by metastatic liver tumor after intra-arterial, intraportal and intravenous administration of BrdU].

To compare the pharmacological advantage of intra-arterial, intraportal and intravenous administration of anticancer drug for metastatic liver tumor, BrdU was administered to rabbits with metastatic liver tumor of VX2 from various routes and taken up into the nuclei of tumor cells. Both one-shot injection and continuous infusion (30 min) of BrdU was performed from celiac artery, portal vein or peripheral vein. In some rabbits, the portal vein or the celiac artery was ligated to form one blood supply to the liver. After the administration of BrdU, the liver was removed. The samples were stained by the immunohistochemical procedure using monoclonal antibody to BrdU. The result was that the drug uptake of small metastatic liver tumor by both arterial and portal one-shot injection was good, and the uptake following intra-arterial injection of BrdU was superior to its intraportal injection in large metastatic tumor. However, only peripheral cells of large tumor took up BrdU after intra-arterial injection and inner cells of large tumor did not take up BrdU after any continuous infusions. The intraportal and intravenous administration of BrdU without ligation of celiac artery had the same effect as its intra-arterial administration.

Animals↗

PubMed1987

Coronary haemodynamic effects of short-term intravenous administration of gallopamil in patients with stable exertional angina.

The effects of short term intravenous administration of gallopamil on coronary haemodynamic variables were studied in 10 patients with stable exertional angina and angiographically confirmed coronary artery disease that affected the proximal portion of the left anterior descending artery. Blood flow in the great cardiac vein was measured by a thermodilution technique, both at rest and during ischaemia induced by atrial pacing, before and after intravenous administration of gallopamil (0.02 mg/kg as a bolus dose given over three minutes, followed by an infusion of 0.0005 mg/kg/min). Gallopamil significantly prolonged the mean (SD) duration of pacing that was tolerated (11 (2.6) vs 14.8 (2.4] min, significantly increased the mean (SD) peak heart rate attained during pacing (142 (15) vs 158 (11) beats/min), and reduced mean (SD) arterial pressure (133 (17) vs 116 (17) mm Hg). There were no changes in mean (SD) blood flow in the great cardiac vein (134.1 (57) vs 112.9 (38) ml/min, mean (SD) anterior regional coronary resistance (1.18 (0.6) vs 1.15 (0.5) mm Hg/ml/min), and mean (SD) anterior regional myocardial oxygen consumption (16.6 (6) vs 13.7 (4) ml/min). These data confirm that gallopamil is an effective antianginal agent and suggest that a reduction of myocardial oxygen demand is the predominant mechanism by which the drug exerts its beneficial effects.

Angina Pectoris↗

PubMed1988

Intersubject variability in plasma theophylline levels after oral and intravenous administration in Jordanian patients with chronic obstructive pulmonary disease.

Plasma theophylline concentrations were determined in 151 Jordanian patients with chronic obstructive pulmonary disease. Mean plasma levels after oral administration were below the therapeutic range and significantly lower than after intravenous administration. Plasma levels in patients with congestive heart failure (CHF) were higher than in patients with no CHF. Trough plasma theophylline concentrations after intravenous administration in patients less than 18 years of age were significantly lower than in those aged 18-60 years. The overall results are in agreement with observations made in other ethnic groups.

Administration, Oral↗

PubMed1994

The response in the blood of piglets to oral doses of galactose and glucose and intravenous administration of galactose.

The kinetics of the response in the blood of piglets to physiological oral intakes of galactose and glucose, and intravenous administration of galactose are described. Following the intravenous administration of galactose to 2- and 10-d-old piglets (n 7), the half-life was 7.98 (SD 0.75) and 7.99 (SD 1.89) min respectively, and efficient elimination rate was 9.09 (SD 2.15) and 8.75 (SD 0.79)% per min respectively. The turnover of galactose in the piglets was 100.3 micrograms/min per kg body weight. These observations demonstrate that galactose was rapidly removed from the blood of the piglets. While the dosing and sampling procedures stimulated hyperglycaemia, they had no effect on the concentration of galactose in the peripheral plasma. The galactose area under the curve (adjusted to the plasma volume of the animal) following a dose of either galactose or galactose plus glucose was 1.75 (SD 0.15) and 1.95 (SD 0.14) arbitrary units respectively in 2-d-old piglets and 1.96 (SD 0.26) and 1.98 (SD 0.10) arbitrary units respectively in 10-d-old piglets. Since the presence of glucose did not lower the adjusted area under the curve for galactose in the peripheral blood, the effect of glucose on the metabolism of galactose in piglets was more like that reported for rats than that for man, guinea-pigs or mice. It is suggested that the galactose moiety of lactose may make an important contribution to the replenishment of liver glycogen in the neonatal piglet.

Administration, Oral↗

PubMed1987

Mechanism of hypocalcemia induced by intraperitoneal, intragastric, and intravenous administration of ethanol to the rat.

Acute hypocalcemic effects of intraperitoneal administration of 3 and 5 g ethanol/kg body weight; intragastric administration of 3, 5, and 7 g ethanol/kg body weight; and intravenous administration of 2.5 a ethanol/kg body weight were investigated in 20 h fasted female Wistar rats. Dose-dependent hypocalcemia was similarly induced by intraperitoneal and intragastric routes of administration. Net calcium efflux from plasma, as indicated by the plasma 45Ca activity, was unaffected by 3 g ethanol/kg body weight but was delayed at higher doses of ethanol. Intragastric, but not intraperitoneal, administration of ethanol increased the gastrointestinal luminal calcium content partly by enhancing calcium secretion. Significantly increased tissue 45Ca content 30 min after ethanol administration was evident in the duodenum (31%), jejunum (27%), and colon (33%) in the intragastric ethanol-treated group and in the duodenum (40%), jejunum (38%), ileum (45%), colon (39%), and liver (25%) in the intraperitoneal ethanol-treated group. Thus, the hypocalcemia induced by both intraperitoneal and intragastric administration of ethanol could be partly accounted for by the suppression of calcium efflux from some soft tissues. In contrast, intravenous administration of ethanol was found to enhance the calcium efflux from plasma without affecting the net 45Ca content in the soft tissues. The mechanism(s) by which ethanol affects calcium transport has yet to be elucidated.

Animals↗

PubMed1987

[Metabolic fate of 14C-isepamicin sulfate (14C-HAPA-B) in rats. I. Absorption, distribution, metabolism and excretion after a single intramuscular and intravenous administration].

Absorption, distribution, metabolism and excretion of 14C-isepamicin sulfate (14C-HAPA-B) following a single intramuscular and intravenous administration of 25 mg/kg were studied in male rats. After an intramuscular administration, the drug was rapidly absorbed and the maximum plasma level of about 75 micrograms/ml was obtained at 10 minutes after the administration. The plasma levels rapidly decreased following either intramuscular or intravenous route. The HAPA-B was rapidly distributed into tissues except the central nervous system and the eye ball. Especially high concentrations were attained in kidney and cartilage tissues, concentrations in lung followed these tissues. Radioactivity remained in kidney for a long period, but it disappeared from cartilage and other tissues rapidly. The radioactivity in kidney was located in the cortex at 24 hours after administration. There was no difference in the distribution of radioactivity with different administration routes. The HAPA-B was mainly excreted in the urine following either intramuscular or intravenous administration. Approximately 80% of the dose by intramuscular and 92% by intravenous administrations were excreted during the first 4 hours. Within 24 hours, over 95% was recovered in either routes. The radioautogram of the thin-layer chromatography of the 0 approximately 16-hour urine showed a single radioactive zone with an identical Rf value to HAPA-B. Binding ratios of 14C-HAPA-B to plasma protein were less than 10% both in vitro and in vivo and to erythrocytes less than 9% in vitro.

Aminoglycosides↗