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At least 19 recordsLinked to original sources

PubMed1999

Amiodarone concentration in human myocardium after rapid intravenous administration.

Intravenous amiodarone has been found useful in the emergent management of life-threatening arrhythmias. Experimental studies have shown that its electrophysiologic effects are proportional to its myocardial concentration. However, early after its intravenous administration, the extent of the concentration of amiodarone in the human myocardium, the site of its action, is not well known. This study was performed to measure the myocardial concentration of amiodarone shortly after rapid intravenous injection. Amiodarone, 150 mg, was injected over 15 seconds intravenously into 9 patients, 52 +/- 9 years of age, weighing between 65 and 98 kg (mean = 81 +/- 15.6). All patients suffered from idiopathic dilated cardiomyopathy, were in NYHA functional class II, and the mean left ventricular ejection fraction was 21 +/- 6%. Right ventricular endomyocardial biopsy, required for the establishment of the diagnosis, was performed 2-5 minutes after drug administration for measurements of its myocardial concentration. Plasma concentrations of amiodarone were also measured at 2, 5, 10, and 60 minutes, and measurements of right heart hemodynamics were made 2 and 10 minutes after the injection. At 2.5 +/- 1.2 minutes after amiodarone administration, the mean myocardial concentration was 95.7 +/- 67.4 micrograms/g (range, 16-175), and the myocardial/plasma amiodarone ratio was 5.05 +/- 5.01. Heart rate increased from 82 +/- 17 to 90 +/- 13 beats/min (P < 0.05), and systolic blood pressure decreased from 132 +/- 19 to 118 +/- 17 mmHg (P < 0.03). The extent of myocardial fibrosis was 5.13 +/- 6.55% (range, 0.3-17.5%). Intravenous amiodarone (150 mg) accumulates rapidly in the human myocardium. This pharmacokinetic characteristic probably explains its acute efficacy in the treatment of life-threatening arrhythmias.

Adult↗

PubMed1987

Ferrite particles: a new magnetic resonance imaging contrast agent. Lack of acute or chronic hepatotoxicity after intravenous administration.

Intravenous administration of ferrite particles may be useful as contrast agents for magnetic resonance (MR) imaging of the liver. We studied several sensitive biochemical parameters of hepatocellular function and toxicity in rats after intravenous ferrite injections to determine whether there was any evidence of iron-induced hepatotoxicity. Light microscopy and iron determinations were performed on the liver, spleen, lung, and kidney. Forty-eight hours after a massive (250 mg iron per kilogram) ferrite injection, liver, spleen, and lung nonheme iron concentrations were markedly increased. Microscopy showed this iron to be entirely in reticuloendothelial cells. Despite the large increase in hepatic iron concentration, we found no evidence of hepatic mitochondrial or microsomal lipid peroxidation or organelle dysfunction, sensitive biochemical indicators of iron-induced hepatocellular injury. At 10 to 11 weeks after administration of ferrite in smaller doses (30 mg iron per kilogram), results of all biochemical and morphologic studies were normal. Furthermore, quantitative iron determinations and microscopic studies suggest that ferrite particles may be partially degraded and that iron is cleared from the liver during a 3-month period. Because ferrite particles are taken up by reticuloendothelial cells, hepatocellular function is not impaired and iron-induced hepatocellular injury does not occur.

Animals↗

PubMed1982

Effect of storage of penicillin-G solutions on sensitisation to penicillin-G after intravenous administration.

Intravenous administration of a total dose of more than 200 million IU of penicillin-G led to sensitisation of lymphocytes and formation of specific anti-penicilloyl antibodies of the IgG class. These effects were prevented when the penicillin solution used was freshly prepared and given as a bolus rather than as a slow infusion. The causative antigens seem to be related not to penicilloylated high molecular weight impurities in the penicillin preparations, but to the degradation and/or transformation products of penicillin-G that form when the drug is in solution even if only for a few hours, and not only at room temperature but also at 4 degrees C. Thus penicillin solutions should be freshly prepared and administered from vials containing less than 10 million IU so that bolus doses can be given.

Adult↗

PubMed1988

The effects of drug metabolism inducers on the delayed neurotoxicity and disposition of tri-o-cresyl phosphate in hens following a single intravenous administration.

Intravenous (iv) administration of tri-o-cresyl phosphate (TOCP) caused a delayed neurotoxic effect in hens similar to that produced by oral and dermal administration. The iv ED50s for producing ataxia and paralysis were estimated to be 15.9 mg/kg and 31.7 mg/kg respectively. The tissue disposition of unaltered TOCP was determined in hens following a single iv injection of 40 mg/kg of TOCP. One hour (hr) after the injection, the leg muscle contained the highest concentration, 26.99 micrograms/g fresh weight followed by the adipose tissue. Among the nerve tissues, the sciatic nerve had the highest concentration, 9.63 micrograms/g followed by the spinal cord and the brain. Except the adipose tissue and the sciatic nerve, the concentration in all analyzed tissues dropped below 1.0 microgram/g (ml) after 24 hr. An unidentified metabolite appeared in bile taken 1 and 3 hr after the injection. Pretreatment of hens with 3-methylcolathrene (3-MC) and beta-naphthoflavone (B-NF) protected against the TOCP-induced delayed neurotoxicity, whereas phenobarbital (PB) failed to protect against the neurotoxicity. Plasma creatine phosphokinase (CK) activity in paralytic birds increased approximately 4 times of the control or symptomless hens on the 21st day. 3-MC-, B-NF- and PB-treatment depressed substantially the concentration of unaltered TOCP in brain and plasma 1 hr after iv dosing with 40 mg/kg of TOCP. Only B-NF pretreatment lowered the level of TOCP in spinal cord. There was no effect of these inducers on the level of TOCP in sciatic nerve and adipose tissue. B-NF and 3-MC lowered significantly the TOCP level in leg muscle, whereas PB had no such effect. More attention should be paid to the role of TOCP in muscle, especially to the leg muscle, judging from the present toxicological and metabolic studies.

Animals↗

PubMed1986

Monitoring of cyclosporin during continuous intravenous administration.

Intravenous cyclosporin was administered continuously to 18 consecutive marrow transplant recipients. Blood samples taken from the single lumen central venous line through which the cyclosporin was administered showed invariably high concentrations. Toxic levels were still present after discontinuation of cyclosporin administration for 8 h, while the peripheral blood levels were in the therapeutic range throughout the observation time. These observations may explain some of the reported discrepancies between the levels of cyclosporin and the side-effects when using intravenous cyclosporin. Mean cyclosporin levels remained stable throughout the 4 weeks of continuous intravenous cyclosporin administration, despite a gradual decrease of the mean cyclosporin dose. Dose adaptations were made based on clinical side-effects and cyclosporin concentrations in blood samples from peripheral veins.

Adolescent↗

PubMed1987

Haemodynamic effects of disopyramide using a new model of intravenous administration.

Intravenous treatment with disopyramide is usually performed by administration of a bolus injection of 150 mg given over 5 min. followed by a continuous infusion of 18-24 mg hour-1. A decrease in cardiac output is associated with this rapid bolus injection. Seven patients with ischaemic heart disease entered an open randomised cross-over trial to elucidate if an extension of the bolus injection time to 20 min. resulted in a smaller decrease in cardiac output. Cardiac index decreased significantly (P less than 0.001) in both situations, with maximum decrease observed at time 5 and 20 min., respectively (equivalent to the ending of the administration of 150 mg disopyramide). The decrease in Cardiac index (mean +/- S.E.M.) was identical in the two situations (2.56 +/- 0.23 to 1.78 +/- 0.21 l/min. X m2 (30%) and 2.66 +/- 0.17 to 1.94 +/- 0.19 l/min. X m2 (27%], respectively. Blood pressure was unchanged, while heart-rate (P less than 0.025) and preejection period index (P less than 0.005) increased significantly and to the same extent in the two situations. Significant correlations between the log free and log total serum concentration of disopyramide and the relative change in preejection period index of r = 0.840 (P less than 0.01) and 0.919 (P less than 0.01), respectively, were observed giving disopyramide over 5 min. A significant anticlockwise hysteresis was observed extending the time of administration to 20 min. As no haemodynamic advantages are achieved by the slower way of administration we would still recommend the bolus injection to be given over 5 min.

Disopyramide↗

PubMed1987

Time-course studies of the distribution of [1-14C]acrylonitrile in rats after intravenous administration.

Intravenous injection of acrylonitrile (ACN) causes adrenal hemorrhagic necrosis. ACN and its metabolites react with glutathione and bind covalently with macromolecules. Hence the purpose of this investigation was to measure the distribution and covalent binding of radiolabel derived from [1-14C]ACN in order to determine whether binding of ACN or its metabolites may be implicated in the pathogenesis of ACN-induced adrenal injury. Following intravenous injections of ACN, concentrations of total radiolabel were highest in the blood, liver, duodenum, kidneys, and adrenals. Except for blood, there was a time-dependent decrease in total radiolabel in these tissues. Compared with other major organ systems, the levels of covalently bound radiolabel were lower in the adrenal glands. These results do not support a role of covalent binding of ACN or its metabolites in the adrenal toxicity of ACN, but suggest that the initial high concentrations of total radiolabelled compounds derived from ACN could play a role in the action of ACN on the adrenal glands.

Acrylonitrile↗

PubMed1981

Pharmacokinetics and tissue distribution of chlorpheniramine in rabbits after intravenous administration.

Intravenous studies of chlorpheniramine (CPM) were conducted in six New Zealand White male rabbits (mean wt. 3.88 kg). CPM and its two demethylated metabolites in arterial serum and urine were assayed by HPLC. Triexponential equations were needed to fit the i.v. CMP serum data in three rabbits, while biexponential equations were required in the other three rabbits. Harmonic mean of V1, Mss, Varea, CL, and terminal t 1/2 were 2.84, 10.8, and 15.5 liters/kg, and 4.14 liters/kg/hr and 2.57 hr, respectively. The average serum protein binding was 44%. The average blood to plasma concentration ratio was 1.85. Estimated mean hepatic blood extraction ratio based on i.v. studies was 0.88. Tissue distribution studies showed rapid and extensive uptake of CPM by various organs such as lung, kidneys, and brain after i.v. bolus injection, and their concentrations were 160-, 80-, and 31-fold higher than the plasma level. The amount of CPM in the muscle was calculated to represent about 50% of CPM present in the body near the steady state. Variation in plasma protein and tissue binding was postulated to be an important factor for the observed marked interspecies difference in the apparent volume of distribution of CPM. Only 2% of the dose was excreted unchanged in the urine.

Animals↗

PubMed1976

[Fluid carbenicillin levels after intravenous administration].

Intravenous infusion of carbenicillin was followed by a determination of the concentration of this antibiotic in both the liquor and serum. The examinations, of which the results are reported in this paper, were made on six patients who had undergone surgical operations to the posterior cranial fossa and on whom lumbar punctures were postoperatively performed every day, as well as on seven hydrocephalic patients where a temporary relief of pressure was obtained by draining excess liquor. The level of carbenicillin in the liquor were found to enable even gram-negative problem germs (e.g., Proteus germs) to be controlled.

Adolescent↗

PubMed1988

[Clinical effectiveness of ethacizine in various methods of intravenous administration].

Intravenous jet injections of 50 mg ethacizine (10 mg/min) are effective in 100% of cases of ventricular extrasystoles, and paroxysms of supraventricular and ventricular tachycardia, and in 59.5% of cases of atrial fibrillation paroxysms. A relationship has been demonstrated between the magnitude of therapeutic effect and the duration of atrial fibrillation as well as the type of underlying disease. The use of the drug is not justified in paroxysmal auricular flutter. Ethacizine is effective in 82.4% of patients with acute myocardial infarction, and in 65% of patients with other diseases. A similar effect was obtained with intravenous drip injections at the rate of 1.7 mg/min, while the incidence of side effects was reduced essentially. Therefore, drip injections of ethacizine are preferable for the treatment of heart rhythm disorders, such as extrasystoles, particularly in patients with acute myocardial infarction.

Adult↗

PubMed1995

Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration.

STUDY OBJECTIVE: To compare placebo vs two different regimens of propafenone administration--intravenous administration or short-term oral loading--in converting recent-onset atrial fibrillation to sinus rhythm. DESIGN: Single-blind placebo-controlled study. PATIENTS: Eighty-seven patients with atrial fibrillation of recent onset (< or = 7 days' duration) admitted to the hospital without signs of organic heart disease (n = 42) or with systemic hypertension without signs or symptoms of heart failure (n = 45). The patients were assigned randomly to treatment with intravenous propafenone (29 patients), oral propafenone (29 patients), or placebo (29 patients). INTERVENTIONS: Administration of propafenone intravenously (2-mg/kg bolus followed by 0.0078 mg/kg/min) or as short-term oral loading (600 mg orally single dose). Patients were submitted to Holter monitoring and conversion to sinus rhythm was evaluated at 1, 3, and 8 h. RESULTS: Conversion to sinus rhythm was obtained within 1 h in 28% with intravenous propafenone, in 3% with oral propafenone, and in 3% with placebo. At 3 h, the efficacy of intravenous propafenone (41%) and of oral propafenone (55%) were statistically superior to placebo (10% of conversions) and at 8 h either intravenous or oral propafenone were effective in almost two thirds of the patients with a statistical difference vs placebo, whose efficacy was 24%. No major side effects were observed. CONCLUSIONS: Propafenone as an oral loading dose is an efficacious and fast way of treating atrial fibrillation of recent onset and due to its simplicity of administration and safety can be preferred to the intravenous route.

Administration, Oral↗

PubMed1981

A new preparation of modified immune serum globulin (human) suitable for intravenous administration. II. Functional characterization.

The commercial immune serum globulin (ISG) product is suitable for use in passive immunization only by intramuscular administration; intravenous use results in vasomotor side reactions. We report the functional characterization of a chemically modified ISG (MISG) that is essentially free of nonspecific complement-binding activity and contains no new antigenic determinants. The half-life values for MISG given intravenously to rabbits, guinea pigs, and humans are shown not to be different from that of ISG. The MISG we describe is shown to fulfill the in vitro and in vivo criteria of stability, safety, function, and half-life, making it suitable for human intravenous administration.

Animals↗

PubMed1997

[Cisplatin/5-fluorouracil intraperitoneal administration superior to intravenous administration for liver metastases of colonic carcinoma].

A 28-year-old female underwent sigmoidectomy for sigmoid colon cancer with peritoneal seeding. One month later, a solitary metastasis was found in S3 of the liver. After CDDP/5-FU intravenous chemotherapy, another metastasis appeared in S7. Intravenous administration showed PD. But the metastatic tumors shrank and became inobservable by CT after the 1st round of CDDP/5-FU intraperitoneal chemotherapy, and S7 tumor could not be identified after the 2nd round. Many previous reports demonstrated the concentration of cytotoxic drug in intraperitoneal administration was much higher than in intravenous administration. Theoretically, intraperitoneal chemotherapy is superior to intravenous chemotherapy for the prevention and treatment of liver metastases. This case demonstrated this hypothesis was right. We think adjuvant intraperitoneal chemotherapy should be re-considered for the prevention of the liver metastases of gastrointestinal cancers.

Adenocarcinoma↗

PubMed1984

[Distribution, metabolism and excretion of 14C-MT-141 in rats. II. Distribution and excretion after multiple intravenous administration in male rats and after single intravenous administration in female rats].

The distribution and tissue accumulation of the radioactivity were studied in male rats after the multiple intravenous administration of 14C-MT-141. The distribution and the placental transfer were also studied using pregnant rats or lactating rats after the single intravenous administration of 14C-MT-141. The radioactive concentration in the fetus was low and the radioactivity was distributed almost uniformly through the fetus body. The peak time of the milk level was 2 hours after the administration and the radioactivity in milk decreased gradually thereafter. The milk levels decreased more slowly than the blood levels did. The blood level after the last dose administered daily for 7 days tended to decrease more slowly, when compared with the single administration. However the blood concentration at 48 hours after the last administration was less than 3 times as high as that after the single administration.

Animals↗

PubMed1996

Pharmacokinetics of the new thyrotropin releasing hormone analogue montirelin hydrate. 2nd communication: distribution and transfer into the fetus and milk after a single intravenous administration and pharmacokinetics and enzyme induction after repeated intravenous administration to rats.

Pharmacokinetics of 14C-labeled montirelin hydrate (CAS 90243-66-6, NS-3) in rats was studied after single or repeated intravenous administration. 1. Radioactivity concentrations in tissues after single administration to male and female rats were highest in the kidney followed (in this order) by plasma, liver, blood, pancreas, uterus (female rats), lung and skin and low in various brain sites 5 min after administration. The concentrations in most tissues were practically parallel to those in plasma over the 24-h period after administration. After decreasing rapidly the concentrations rose slightly for 10 h and then decreased gradually. 2. Five min after single administration to male rats, the concentration of the main metabolite CNK-6004 (deamidated product) was lower in the plasma, but higher in the liver and kidney than the NS-3 concentration. From 0.5 to 2 h after administration, the concentration of CNK-6004 was higher than that of NS-3 in the plasma, liver and kidney, accounting for 33-64% of the radioactivity concentration. 3. After administration to rats on the 18th day of pregnancy, the radioactivity concentrations in the fetal whole body and fetal tissues peaked later than those in the maternal plasma, tissues and placenta. The maximum concentration in the fetal tissues was 2% or less of that in the maternal plasma. 4. After administration to lactating rats, the radioactivity concentration in milk reached the maximum 10 h after administration, and decreased gradually in parallel with the concentration in the plasma 24 to 168 h after administration. 5. During repeated once daily administration for 10 days, the radioactivity concentration in the plasma 24 h after each administration reached practically steady state level after the 7th administration and decreased with a half-life of 38.1 h after the last administration. 6. The radioactivity concentrations in most tissues after the last administration were not significantly different from those after a single administration. Decreased elimination of the radioactivity was observed in the white fat and skin, in which radioactivity levels were higher than those in the other tissues a long time after the last dose. 7. Excretion of the radioactivity in the urine and feces during repeated administration was constant after the 2nd administration. The excretion by 168 h after the last administration was 66.9 and 14.3% of the cumulative dose in the urine and feces, respectively (total: 81.2%). 8. The composition of metabolites in the plasma, liver, kidney and urine after the last administration did not differ markedly from that after a single administration. Once daily repeated administration for 7 days had no effect on the liver drug metabolizing enzyme activities.

Animals↗

PubMed1985

Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep.

The pharmacokinetics of deoxynivalenol (DON) were studied in sheep after administrating intravenous and oral doses (0.5 and 5.0 mg/kg, respectively). The plasma concentrations were measured using an electron-capture gas chromatographic method. After iv administration DON plasma levels were found to decrease biexponentially, showing a rapid distribution phase (t 1/2 alpha = 12-23 min), followed by a slower elimination phase (t 1/2 beta = 57-78 min). Only trace levels of DON could be detected in plasma 7 hr post-dosing. Further pharmacokinetic data suggest that DON was confined mainly to extracellular fluid, and did not appear to undergo any significant binding or uptake by tissue. After oral dosing, DON was quickly absorbed (t-max 4.0-5.3 hr), but had a systemic bioavailability of only 7.5%; due in part to its rapid and efficient metabolism by rumen microorganisms. Half-life of elimination (t 1/2 beta) was 100-125 min following oral administration, and depending on the animal, required 20-30 hr to be cleared from the system. The metabolic formation of the glucuronide conjugate after iv and oral administration of DON appeared to occur quite efficiently (iv, 21%; oral, 75%), and its elimination half-lives (iv, 150-200 min; oral 6.1-7.1 hr) were considerably longer than that of the parent toxin. Detection in plasma of the de-epoxide metabolite, DOM-1, accounted for only a minor portion of the dose after either dosing regimen (iv, less than 2.0%; oral, less than 0.3%), occurring predominantly as the glucuronide conjugate.

Administration, Oral↗

PubMed1995

Pharmacokinetics of human activated protein C. 2nd communication: tissue distribution study of a lyophilized purified human activated protein C after single or repeated intravenous administration in male mice and placental transfer and milk passage study after intravenous administration in pregnant and lactating mice.

Tissue distribution studies of human activated protein C (CAS 42617-41-4, APC) were performed in mice after single or repeated administration, and placental transfer and milk passage study were investigated. At 15 min after a single intravenous administration of 125I-APC, radioactivity was mainly distributed to the blood and blood rich organ, such as liver, and then rapidly eliminated. The radioactivity distributed to tissues was almost negligible at 24 h after administration except for the thyroid. The qualitative study of the distribution of radioactivity to tissues by whole body autoradiography demonstrated the correspondence to the result of the quantitative assay of distribution of radioactivity after single administration of 125I-APC. The influence of repeated administration of APC on its pharmacokinetic disposition was studied by administering 125I-APC once a day to mice for 14 days. Though plasma radioactivity at 15 min in mice during repeated administration of 125I-APC was almost similar to that at 15 min after a single administration, the radioactivity at 24 h after administration was 2 times higher than that after a single administration. The profile of plasma radioactivity during and after repeated administration corresponded to the simulation curve which was described with the pharmacokinetic parameters obtained previously after the single administration. Distribution profile after repeated administration at 15 min after the 4th, 7th, 10th and 14th administration was almost similar to that at 15 min after a single administration except for the thyroid and spleen. In the thyroid, the radioactivity was 500 times higher than that after a single administration, and HPLC analysis demonstrated that the radioactivity was attributed to thyroglobulin. As to the spleen, the radioactivity was about 52% of that after a single administration. During the repeated administration, the spleen became larger than that after a single administration and the final weight was 2 times heavier than that of the non-treated animal. The decrease in radioactivity of the spleen during repeated administration was attributed to the hypertrophy of the organ. Placental transfer of 125I-APC was studied with pregnant mice quantitatively and qualitatively. Radioactivity distributed in fetuses was low at every point examined, and the result corresponded to the autoradiography. During lactation, radioactivity transferred to milk and milk to plasma ratio reached 5.7 after intravenous administration of 125I-APC. HPLC analysis of the milk radioactivity demonstrated that most of the radioactivity was present in the macromolecules produced by the lactating mother.

Animals↗

PubMed1997

Toxicologic effects of an oligodeoxynucleotide phosphorothioate and its analogs following intravenous administration in rats.

The aim of the present study is to evaluate the in vivo toxicologic effects of a phosphorothioate oligodeoxynucleotide (PS oligo) and three of its analogs [PS oligo containing four methylphosphonate linkages at the 3' and 5'-ends (MBO 1), PS oligo containing four 2'-O-methylribonucleosides at both the 3'- and 5'-ends (MBO 2), and PS oligo containing an 8 bp loop region at the 3'-end (self-stabilized oligo)]. Oligodeoxynucleotides were administrated intravenously to male and female rats at doses of 3, 10, and 30 mg/kg/day for 14 days. Rats were killed on day 15, blood samples were collected for hematology and clinical chemistry determinations, and tissues, including lymph nodes, spleens, livers, and kidneys, were subjected to pathologic examinations. The toxicity profiles of the four oligodeoxynucleotides were very similar, but differed in magnitude. In terms of the severity of the abnormalities caused by the oligodeoxynucleotides, the order was MBO 2 > PS oligo > self-stabilized oligo > MBO 1. Alterations in hematology parameters included thrombocytopenia, anemia, and neutropenia. Abnormalities in clinical chemistry parameters observed with PS oligo or MBO 2 were dose-dependent elevation of liver transaminases and reduction of the levels of alkaline phosphatase, albumin, and total protein. In addition, MBO 2 caused elevation of the total bilirubin level in male rats at the 30 mg/kg dose. No major alterations in hematology or clinical chemistry were observed in rats receiving MBO 1 or self-stabilized oligo. Dose-dependent enlargements of spleen, liver, and kidney were observed, especially in rats receiving PS oligo and MBO 2. Pathologic studies showed a generalized hyperplasia of the reticuloendothelial (RE) system in the tissues examined. Alterations in the spleen were mainly RE cell hyperplasia and hematopoietic cell proliferation. In addition to RE cell hyperplasia, lymph nodes showed necrosis, hepatocytes showed cytologic alterations and necrosis, and kidneys showed renal tubule regeneration. The severity of pathologic changes observed was oligodeoxynucleotide dependent, in the order of MBO 2 > PS oligo > self-stabilized oligo > MBO 1.

Animals↗