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At least 973 records · Page 54Linked to original sources

Continuous deep intravenous infusion in rabbit embryotoxicity studies.

1. This investigation was undertaken to evaluate the suitability of an intravenous infusion technique in the pregnant rabbit. 2. 18 New Zealand White rabbits were anaesthetised on day 1 of gestation and an indwelling catheter was implanted into the superior vena cava by introduction into the jugular vein. The catheter was attached by a tether system to a remote infusion pump. 3. The pregnant rabbits were infused with physiological saline at a rate of 4 ml kg-1 day-1 until day 19 of gestation. A caesarean examination was performed on day 29 of gestation. The results obtained were compared with historical control data from 150 mated rabbits. 4. Anaesthesia and catheter implantation caused a slight transient reduction in maternal food consumption and weight gain. Pregnancy rate, pre-implantation loss and early resorption incidence were not affected. 5. Late resorption incidence and post-implantation loss were higher in the infused group by comparison with the historical controls but the individual data did not suggest an effect of treatment. Foetal weight was not adversely influenced. Three of the infused dams each contained one malformed foetus: a possible influence of infusion in the aetiology of these abnormalities cannot be excluded nor confirmed within the limitations of this experiment.

Animals↗

Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion.

In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain-deleted human factor VIII (hFVIII) gene. Infusions were well tolerated. Tests for replication competent retrovirus have been negative. Polymerase chain reaction (PCR) analyses demonstrate the persistence of vector gene sequences in peripheral blood mononuclear cells in 3 of 3 subjects tested. Factor VIII was measured in serial samples using both a one-stage clotting assay and a chromogenic assay. While no subject had sustained FVIII increases, 9 subjects had FVIII higher than 1% on at least 2 occasions 5 or more days after infusion of exogenous FVIII, with isolated levels that ranged from 2.3% to 19%. Pharmacokinetic parameters of exogenous FVIII infused into subjects 13 weeks after vector infusion showed an increased half-life (T1/2; P <.02) and area under the curve (AUC, P <.04) compared with prestudy values. Bleeding frequency decreased in 5 subjects compared with historical rates. These results demonstrate that this retroviral vector (hFVIII(V)) is safe and, in some subjects, persists more than a year in peripheral blood mononuclear cells, with measurable factor VIII levels and with increased available FVIII activity (increased T1/2 and AUC) after infusion of exogenous FVIII concentrate.

Adolescent↗

[A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs].

A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50 and 100 mg/kg/hr in female beagle dogs was conducted. No death occurred in any group. Changes attributable to the treatment with magnesium sulfate were decreased food consumption and body weight gain, anemic change, increased urine volume, decreased serum calcium level, increased inorganic phosphorus level, slight prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the group treated with 100 mg/kg/hr. In addition, essentially similar changes were also observed at the same dosage level in the 2-week study of this drug, in which recoverability was recognized with 2-week follow-up observation after drug withdrawal. In conclusion, the nontoxic dosage level was judged to be 50 mg/kg/hr under the condition of the present study.

Anemia↗

Protracted intravenous infusion of 5-fluorouracil in combination treatments. A review.

5-fluorouracil (5-FU) administered by protracted intravenous infusion has been shown to have clinical utility against colorectal cancer and several other advanced tumors. However, additional therapeutic strategies are needed to further improve treatment results. Although the addition of low-dose cisplatin appeared to improve the clinical activity of 5-FU infusion in early phase II studies, subsequent evaluation has failed to substantiate these early reports. In addition, toxicity has been significantly increased. Combinations of cisplatin and other drugs with 5-FU infusion are currently being evaluated. Phase I studies demonstrate that only low doses of concomitant leucovorin are necessary to potentiate 5-FU infusion; phase II studies to evaluate efficacy are underway. Although combinations of 5-FU and biological therapies such as alpha 2a-interferon appear to be very promising, they will require extensive phase II and III testing to define their clinical utility and toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Stability of ranitidine hydrochloride at dilute concentration in intravenous infusion fluids at room temperature.

The stability of ranitidine at low concentration (0.05 mg/mL) in five intravenous infusion solutions (0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose with 0.45% sodium chloride, and 5% dextrose with lactated Ringer's injections) was studied. Admixtures were stored for seven days at room temperature in 150-mL and 1-L polyvinyl chloride infusion bags. Ranitidine stability in 0.9% sodium chloride injection and in 5% dextrose injection was also examined for up to 28 days, and these data were compared with data obtained at higher ranitidine concentrations (0.5-2.0 mg/mL). At intervals during the storage periods, color, clarity, and solution pH were examined and ranitidine content was determined by a stability-indicating high-performance liquid chromatographic assay. Ranitidine content remained greater than 90% of the initial concentration for more than 48 hours in all infusion fluids except 5% dextrose with lactated Ringer's injection. No visual changes or appreciable changes in pH were observed for any of the solutions. At the dilute concentration, ranitidine was markedly more stable after eight hours in 0.9% sodium chloride injection than in 5% dextrose injection. In 0.9% sodium chloride injection, ranitidine concentrations remained above 95% for up to 28 days, but drug concentrations in 5% dextrose injection fell below 90% after seven days. Stability in 5% dextrose injection improved as ranitidine concentrations increased from 0.05 to 2.0 mg/mL. Ranitidine (0.05 mg/mL) is stable for at least 48 hours at room temperature in all infusion fluids tested except 5% dextrose with lactated Ringer's injection.

Chromatography, High Pressure Liquid↗

[Cutaneous necrosis and rhabdomyolysis following the intravenous infusion of vasopressin].

We describe the case of a patient with hepatic cirrhosis treated with an intravenous infusion of vasopressin to control an upper digestive hemorrhage, who developed distance cutaneous necrosis and rhabdomyolysis. We review the other cases published in the international scientific literature and we discuss the possible pathogeny of these complications.

Gastrointestinal Hemorrhage↗

Treatment of Alzheimer disease by continuous intravenous infusion of physostigmine.

Physostigmine, a reversible and nonselective cholinesterase inhibitor, administered by steady-state, continuous intravenous infusion to carefully selected subjects with mild-moderate Alzheimer disease, produced significant but modest improvement in memory in five of nine subjects. Drug dosing was limited by the occurrence of adverse effects. Apparent tolerance to adverse effects was observed in two subjects when the dose of physostigmine was escalated slowly over at least 2 weeks. Steady-state cholinesterase inhibition by physostigmine appears to produce sustained cognitive improvement in some subjects with Alzheimer disease without substantially altering its therapeutic index.

Aged↗

Effect of continuous intravenous infusion of secretin preparation (secrepan) in patients with hemorrhage from chronic peptic ulcer and acute gastric mucosal lesion (AGML).

The purpose of the present study was to investigate the hemostatic effect of continuous intravenous infusion of secrepan (secretin preparation, Eisai Company Ltd. Tokyo) on gastroduodenal hemorrhage in patients with chronic peptic ulcer and AGML (acute gastric mucosal lesion). The patients consisted of 37 cases of bleeding ulcer (13 cases of chronic peptic ulcer and 24 cases of AGML). Secrepan was infused at a rate of 2 U/kg/hr for the first 3 days and 0.5 U/kg/hr for the next 4 days. The cumulative hemostatic rate in the chronic peptic ulcer group was 53.9% after 36 hours, and 76.9% after 48 hours of infusion, but no significant change in rate was observed thereafter. The cumulative hemostatic rate in the AGML group was 52.2% after 36 hours, and 95.7% after 72 hours of infusion. The hemostatic rate in chronic peptic ulcer and AGML cases with only slight or moderate bleeding was 100%, and no recurrent hemorrhaging was observed. The hemostatic rate in chronic peptic ulcer cases with severe bleeding was 62.5% and in AGML cases with severe bleeding was 93.3%, and 7 of 15 cases showed recurrent hemorrhage. Our findings indicated that continuous intravenous infusion of secrepan had more favorable effects on AGML cases, than on chronic peptic ulcer cases.

Acute Disease↗

Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease.

Adenosine is an endogenously produced compound that has significant effects as a coronary and systemic vasodilator. Previous studies suggest that intravenous infusion of adenosine, coupled with thallium-201 scintigraphy, may have specific value as a noninvasive means of evaluating coronary artery disease. The purpose of this study was to compare the diagnostic value of adenosine thallium testing with that of standard exercise thallium testing. One hundred subjects were studied with exercise thallium imaging and thallium imaging after adenosine infusion, including 47 with angiographically proved coronary artery disease and 53 control subjects. The overall sensitivity of the thallium procedures was 81% for the exercise study and 83% for the adenosine study (p = NS); the specificity was 74% for the exercise study and 75% for the adenosine study (p = NS). The diagnostic accuracy of the exercise study was 77% and that of the adenosine study was 79%. Ninety-four percent of subjects had an adverse effect due to the adenosine infusion; however, most of these effects were mild and well tolerated. All adverse effects abated within 30 to 45 s of the termination of the study, consistent with the very brief half-life of the agent. Thus, thallium-201 scintigraphy after intravenous infusion of adenosine has a diagnostic value similar to that of exercise thallium testing for evaluation of coronary artery disease. Adenosine thallium testing may be particularly useful in evaluating patients unable to perform treadmill exercise testing.

Adenosine↗

Accuracy of intravenous infusion pumps in continuous renal replacement therapies.

Most extracorporeal continuous renal replacement therapies (CRRT) require inflow pumping of either dialysate, filtrate replacement solution, or both. Outflow of spent dialysate and ultrafiltrate can be accomplished by gravity drainage or pump. Intravenous infusion pumps have been commonly used for these purposes, although little is known about the accuracy of these pumps. To evaluate accuracy of two different types of intravenous infusion pumps used in CRRT, we studied flow rates at nine different pressure variations in three piston type and three linear peristaltic pumps. The results showed that error of either pump was not different for flow rates of 4 and 16 ml/min. Both types of pumps were affected by fluid circuit pressures, although pressure conditions under which error was low were different for each pump type. The linear peristaltic pumps were most accurate under conditions of low pump inlet pressure, whereas piston pumps were most accurate under conditions of low pump pressure gradient (outlet minus inlet) of 0 or -100 mmHg. The magnitude of error outside these conditions was substantial, reaching 12.5% for the linear peristaltic pump when inlet pressure was -100 mmHg and outlet pressure was 100 mmHg. Error may be minimized in the clinical setting by choosing the pump type best suited for the pressure conditions expected for the renal replacement modality in use.

Equipment Design↗

Intravenous infusion of glucose and insulin in relation to milk secretion in the sow.

1. A comparison was made of the composition of milk from front and rear tetas in four sows. There were small and not significant differences in fat, protein and lactose contents, and in the fatty-acid composition of the milk fat with the exception of the 18:3 acid where the difference was also small but significant. 2. The effects of intravenous infusions of glucose and insulin in lactating sows on milk secretion and blood composition were investigated in two sows. 3. Intravenous infusion of glucose had no effect on blood plasma glucose concentration but increased the yields of lactose, protein and water. 4. Intravenous infusion of insulin depressed plasma glucose concentration and the yields of lactose and water. The yield of protein was unaffected. 5. It is concluded that differences between the non-ruminant (the sow) and the ruminant in the responses in milk secretion to glucose infusion may be related to differences in the sensitivity to insulin of mammary tissue.

Animals↗

Miconazole sorption to intravenous infusion sets.

The sorption of the antifungal drug miconazole onto the plastics of infusion bags and intravenous administration sets has been investigated. HPLC methodology was applied for the determination of miconazole concentrations. The results obtained indicate that the sorption of miconazole is low and is unlikely to result in significant loss of clinical efficacy.

Adsorption↗

Intravenous infusion of lipid for the prevention of essential fatty acid deficiency in premature infants.

This study was designed to determine the amount of linoleic acid required to prevent essential fatty acid deficiency in premature infants. This was achieved by infusing 1 g intravenous lipid.kg-1.d-1 over 18-20 h beginning on day 2 and increasing by 0.5 g.kg-1.d-1 to a maximum of 3 g.kg-1.d-1. The actual mean amounts of linoleic acid administered (mg/kg) were 613 on day 2, 767 on days 3 and 4, 862 on day 5, and 1062 on day 6. None of the neonates managed in this fashion showed a high triene-tetraene ratio on days 3 or 7 (in contrast to control subjects, 80% whom were abnormal). Plasma triglycerides and nonesterified fatty acids (NEFAs) increased during the infusions but not to concentrations indicative of fat intolerance. The rise in NEFAs was associated with evidence of bilirubin displacement from circulating albumin but this occurred to only a modest degree.

Bilirubin↗

Zatebradine: pharmacokinetics of a novel heart-rate-lowering agent after intravenous infusion and oral administration to healthy subjects.

Zatebradine (1; UL-FS 49 CL; 1,3,4,5-[tetrahydro-7,8-dimethoxy-3-[3-[ [2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-2H-3-benzazepin- 2-on- hydrochloride) is the proposed INN name for a nonchiral, novel, specific heart-rate-lowering drug that is suitable for the treatment of stable angina pectoris. The pharmacokinetics of 1 and of total radioactivity in healthy volunteers (n = 6) were determined after intravenous infusion and oral administration of an experimental drug solution containing 7.5 mg (1.85 MBq) of 14C-labeled drug. Concentrations in plasma and urine were measured by a specific, sensitive, reversed-phase automated high-performance liquid chromatography system with fluorimetric detection at 285 nm Ex, 315 nm Em and by liquid scintillation counting. Recovery of total radioactivity was 89.8 +/- 2.3% (infusion) and 92.2 +/- 3.0% (oral). Renal elimination of total radioactivity was 62.5 +/- 2.0% (infusion) and 48.8 +/- 3.1% (oral). After intravenous infusion and oral administration, 27.3 +/- 2.4 and 43.4 +/- 3.9%, respectively, of the administered dose was eliminated in the feces. Absorption, based on renal excretion of total radioactivity following oral and intravenous dosing, was 79.2 +/- 15.3% (mean +/- standard deviation). Unchanged parent drug contributed 28.4 +/- 5.8% (infusion) and 12.4 +/- 3.7% (oral) of the dose to renal excretion. Zero to three minutes after cessation of the 20-min infusion, the maximum concentration of parent drug in plasma was 161.9 +/- 70.9 ng/mL. After oral administration, a mean peak concentration in plasma of 24.3 +/- 6.7 ng/mL (0.5-3 h postadministration) was reached. Data regarding levels of 1 in plasma could be adequately fitted with an open, two-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable route than intravenous administration as a systemic chemotherapy. A comparative pharmacokinetic analysis of platinum using a new mathematical model after intraperitoneal vs. intravenous infusion of carboplatin--a Sankai Gynecology Study Group (SGSG) study.

OBJECTIVE: To clarify the pharmacological advantage of carboplatin-based intraperitoneal chemotherapy using the three-compartment mathematical model. METHODS: Eleven consecutive patients in one institution underwent intraperitoneal administration of carboplatin, and 11 consecutive patients in another institution received intravenous administration. Carboplatin (AUC=6 mg x min/ml) was diluted in 500 ml 5% glucose and administered either as an intraperitoneal bolus infusion or intravenous drip infusion during 1 h. Patients undergoing intravenous injection also received an infusion of 500 ml 5% glucose to obtain intraperitoneal samples. Intraperitoneal fluid and blood samples were obtained, immediately and 1, 2, 4, 8, 12, and 24 h after administration. The mathematical model consisting of a three-compartment model was applied to analyze the pharmacokinetics. The model was created with simultaneous differential equations and was solved by the Runge-Kutta method. RESULTS: The rate constants of platinum diffusion from the peritoneal cavity to serum, serum to peritoneal cavity, serum to peripheral space, peripheral space to serum, and elimination were 0.94+/-0.79 (mean+/-SD), 1.28+/-2.50, 16.50+/-9.26, 0.99+/-0.62, and 4.14+/-1.45 (h-1), respectively. When the theoretical pharmacological concentration of platinum was calculated using this mathematical model, 24-h platinum AUC in the serum was exactly the same regardless of intraperitoneal or intravenous administration of carboplatin. However, the 24-h platinum AUC in the peritoneal cavity was approximately 17 times higher when carboplatin was administered by the intraperitoneal route. CONCLUSION: The present pharmacological analysis suggests that intraperitoneal infusion of carboplatin is feasible not only as an intraperitoneal regional therapy but also as a more reasonable route for systemic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Initial 48-hour acid inhibition by intravenous infusion of omeprazole, famotidine, or both in relation to cytochrome P450 2C19 genotype status.

BACKGROUNDS AND AIMS: Faster and stronger acid inhibition is required for the treatment of hemorrhage from peptic ulcers. We compared the effects of intravenous infusion regimens of a proton pump inhibitor (PPI) alone, a histamine 2 receptor antagonist (H2RA) alone, and the combination of a PPI with an H2RA on acid inhibition in the early postadministration phase in relation to cytochrome P450 (CYP) 2C19 genotype status. METHODS: Fifteen Helicobacter pylori-positive volunteers with 3 different CYP2C19 genotypes were administered twice-daily intravenous infusions of 20 mg famotidine alone, 20 mg omeprazole alone, 10 mg omeprazole plus 10 mg famotidine (half-concomitant regimen), and 20 mg omeprazole plus 20 mg famotidine (full-concomitant regimen) for 2 days. The subjects underwent 48-hour intragastric pH monitoring. RESULTS: In homozygous extensive metabolizers (EMs) the median first 24-hour intragastric pH with the full-concomitant regimen was 4.8 (range, 4.5-5.4), which was significantly higher than that with omeprazole alone (3.9 [range, 2.6-4.7], P=.043) or famotidine alone (4.4 [range, 3.8-4.9], P=.043). In heterozygous EMs and poor metabolizers the respective median first 24-hour pH values attained with omeprazole alone (5.8 [range, 4.3-6.3] and 6.1 [range, 5.3-7.4]) and the full-concomitant regimen (5.8 [range, 5.1-6.4] and 5.8 [range, 5.4-6.2]) were significantly higher than those attained with famotidine alone (4.1 [range, 3.9-6.5] and 4.7 [range, 3.7-5.7], P=.043 for all). CONCLUSIONS: For faster and stronger acid inhibition, the concomitant infusion regimen of a PPI and an H2RA appears to be therapeutically useful in homozygous and heterozygous EMs, but omeprazole alone appears to be sufficient in poor metabolizers of CYP2C19.

Adult↗

Gaucher's disease: lack of antibody response in 12 patients following repeated intravenous infusions of mannose terminal glucocerebrosidase.

An amplified ELISA has been employed for monitoring the safety of repeated intravenous infusions of modified human placental glucocerebrosidase. The enzyme infusions consisted of biweekly injections of macrophage targeted glucocerebrosidase over a 6 month duration. Serum samples collected throughout the study were assayed by use of an ELISA using alkaline phosphatase coupled to alcohol dehydrogenase for amplification. Using this protocol, 0.2-5 ng affinity purified immunoglobulin specific for glucocerebrosidase can be detected. Occasional false positives necessitate multiple repeat assays over time to accurately assess immunogenic response. Blinded ELISAs were performed on sera from both infused patients with Gaucher's disease and uninfused control patients and compared with apparent immunoglobulin concentration in 54 normal control sera. Although several samples showed apparently elevated immunoglobulin levels, repeat analyses failed to demonstrate high levels reproducibly. Furthermore, these sera were unable to neutralize enzyme or to precipitate radiolabelled enzyme, confirming the absence of antibody. Problems with high sensitivity ELISA formats are discussed.

Animals↗

Pharmacokinetics and nephrotoxicity of continuous intravenous infusion of gentamicin in low birth weight infants.

We evaluated the pharmacokinetics and renal effects of continuous intravenous infusion of gentamicin compared with multiple-dose therapy given in equivalent daily amounts. Nine infants (mean gestational age 34.7 weeks, mean birth weight 2107 gm) were given intermittent injections of gentamicin and 10 infants (mean gestational age 34.8 weeks, mean birth weight 2078 gm) received gentamicin by continuous infusion. Comparison of gentamicin pharmacokinetic data revealed a larger volume of distribution and AUC, prolonged terminal t1/2, and slower total body clearance of the drug in those infants receiving gentamicin by continuous infusion. During and after therapy the fractional excretion of sodium was significantly increased in the continuous infusion group. After treatment the creatinine clearance and excretion of beta 2-microglobulin were significantly lower in the continuous therapy group. Our results indicate that infants receiving gentamicin by constant infusion are at higher risk of nephrotoxicity. The extent of this nephrotoxic hazard remains to be determined.

Creatinine↗