[Intravenous infusion of molsidomine in infarct therapy].
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Aged↗
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Results for “Infusions, Intravenous”
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Liver sinusoidal lymphocytes return to liver after intravenous infusion.
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Animals↗
Systemic and pulmonary haemodynamic effects of intravenous infusion of non-ionic isoosmolar dimeric contrast media. An investigation in the pig of two ratio 6 contrast media.
The systemic and pulmonary haemodynamic effects of i.v. infusion (1 ml/s) of high doses (4 ml/kg) of 2 non-ionic, isoosmolar dimeric contrast media (CM) were investigated in 17 female pigs. The 2 CM were iodixanol and iotrolan. Both CM induced a significant increase of the following parameters: mean arterial, mean right atrial, mean pulmonary arterial, mean pulmonary arterial occlusion pressure, cardiac output, stroke volume, and diuresis. The plasma concentration of atrial natriuretic peptide was significantly increased following infusion of the 2 CM. A significant decrease was seen in the systemic and pulmonary vascular resistance.
Animals↗
Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion.
Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.
Adult↗
Cutaneous, musculoskeletal and bone flow scintiscan by intravenous infusion of 99mTc-MDP (Diphosphonate) in the evaluation and control of patients treated with spinal cord stimulation for ischaemic pain.
In patients affected by unbearable pain secondary to peripheral vascular disorders beyond surgical repair such as thromboangitis obliterans, diabetic microangiopathy, arteriosclerosis obliterans, there is a need to establish the degree of micro-circulation functionality before proceeding with invasive pain therapy, such as Spinal Cord Stimulation (SCS). From our series some cases of refractory ischaemic pain subjected to nuclear medicine techniques assessment before and after SCS implant will be presented; these data suggest that the use of radionuclides for quantifying regional perfusion, in view of the information it offers us both in the dynamic angiographic phase and in the later static phase, constitutes a very valid aid in the diagnosis and treatment of chronic pain conditions of ischaemic origin. Cutaneous, musculoskeletal and bone flow scintiscan is a non-invasive procedure which allowed us to make an objective selection of patients who are candidates for prolonged conservative treatment thus limiting the incidence of ineffective permanent SCS implants.
Adult↗
[Efficacy of the treatment of gastric cancer as neo-adjuvant chemotherapy of 48 hour continuous intravenous infusion of 5-fluorouracil (5-FU) with leucovorin (LV)].
A 51-year-old female with inoperable gastric cancer and with infiltration of pancreatic tail diagnosed by abdominal CT was treated with leucovorin (LV) and 5-fluorouracil (5-FU). The regimen was: LV 30 mg/body/24 hr prior to 5-FU 1,000 mg/m2/day for 48 hrs. This treatment was repeated 6 times. After treatment, the size of tumor decreased so that the patient was able to be operated (Total gastrectomy with partial distal pancreatico-splenectomy). During the treatment, patient showed no side effect except for slight nausea. This neo-adjuvant chemotherapy might be a recommendable treatment of advanced gastric cancer.
Adenocarcinoma↗
[Continuous intravenous infusion of ritodrine using a portable balloon pump].
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Adult↗
[A double-blind comparison of FUra plasma concentration by oral (UFT) vs continuous intravenous infusion (5-FU)].
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Administration, Oral↗
Pharmacokinetics of recombinant human interleukin 3 administered subcutaneously and by continuous intravenous infusion in patients after chemotherapy for ovarian cancer.
Twenty chemotherapy-naive patients with ovarian carcinoma received 1, 5, 10, or 15 micrograms/kg/day (five patients per dose step) of recombinant human interleukin 3 (rhIL-3) over 7 days after carboplatin/cyclophosphamide in Cycles 1 and 3. Patients received rhIL-3 by continuous i.v. infusion or once daily s.c. injection in Cycle 1 and the alternate route in Cycle 3. Plasma rhIL-3 samples were obtained once daily on Days 1 to 6 and serially over a 24-h period on Day 7 for pharmacokinetic assessment of s.c. and i.v. administered rhIL-3 in 16 and 17 patients, respectively. Concentrations were assayed by a time-resolved fluorescence sandwich immunoassay. Pharmacokinetic parameters were derived by noncompartmental methods. Mean steady-state concentrations during continuous i.v. infusion ranged from 117 pg/ml (1 microgram/kg/day) to 2217 pg/ml (15 micrograms/kg/day) and were linearly related to dose (r = 0.87, P < 0.001). When dose normalized, the mean steady-state concentrations were comparable at all doses. The total-body clearance was approximately 4 to 5 ml/min/kg. Elimination half-life (t1/2 i.v.) could be assessed for the 5- to 15-micrograms/kg/day dose levels and was 53, 41, and 26 min for the 5-, 10-, and 15-micrograms dose levels, respectively (not significant between dose levels). Following s.c. injection, the maximum rhIL-3 plasma concentration ranged from 206 pg/ml (1 microgram/kg/day) to 6930 pg/ml (15 micrograms/kg/day). Both the maximum measured plasma concentration (r = 0.89, P < 0.0001) and the area under the plasma concentration/time curve (r = 0.93, P < 0.0001) were related to dose. Dose-normalized values were comparable over the entire dose range. Elimination t1/2s.c. was 4.8 h at the 1-microgram dose level and roughly half this time for the 5- to 15-micrograms/kg/day dose levels. The systemic clearance of approximately 5 to 6 ml/min/kg was comparable at all dose levels. Based on trough levels of the 7-day s.c. course, no rhIL-3 accumulation occurred. Bioavailability of s.c. administered rhIL-3 was nearly 100%. No correlation between creatinine clearance and pharmacokinetic parameters of rhIL-3 could be demonstrated. Since there was also no difference in hematological efficacy between the two routes of rhIL-3 administration, we conclude that the s.c. route of administration appears to have no disadvantages over the i.v. route and may facilitate its clinical application.
Adolescent↗
[The resolution of right atrial thrombosis of recent onset during the intravenous infusion of rtPA: a report of 3 cases with continuous echocardiographic monitoring].
We performed continuous echocardiographic examination during the i.v. administration of rtPA in three patients with recent-onset, mobile right atrial thrombosis, in order to assess both the timing and mode of thrombus resolution. In all these cases, right atrial thrombus disappeared before the scheduled dose (100 mg i.v. within three hours) was completed: 60 mg of rtPA were required in the first patient, and 50 mg in the other two. In the first case, the thrombus divided into numerous smaller fragments chaotically moving in the right chambers before disappearing; in the second, the echo reflectivity of the thrombus gradually diminished and the mass showed multiple echo-lucent cavities before disappearing; in last case, the atrial mass migrated from the right atrium to the right ventricle before disappearing. None of the patients experienced any symptoms at the dissolving of the thrombus; bleeding complications occurred in all three (in one, at the site of previous PTCA; in another, at the site of arterial and venous puncture; in the third the haematoma was localized at the site of a previous orthopedic operation) but only two required blood transfusion. In patients with right atrial thrombosis, continuous echocardiographic examination allows us to identify both the timing and mode of thrombus resolution, and the occurrence of new-onset peripheral pulmonary embolization. This information can help in optimizing the dosage of the drug in patients in whom bleeding complications can be suspected to occur after thrombolytic therapy.
Aged↗
In vivo desensitization to leukotriene B4 (LTB4) in the rabbit. Inhibition of LTB4-induced neutropenia during intravenous infusion of LTB4.
Bolus injections of leukotriene B4 (LTB4) at 30-min intervals repeatedly induced similar profound and reversible neutropenias. In contrast, after a 30-min infusion of LTB4, the neutropenia induced by bolus injections of LTB4 was inhibited in a dose-dependent manner; a threshold inhibition was seen at the infusion rate of 10 ng LTB4/min/kg, whereas almost complete inhibition was observed at 50 ng LTB4/min/kg. Steady state arterial plasma concentrations of LTB4 increased proportionally to LTB4 infusion rate, ranging from 0.15 +/- 0.01 nM (control) to 2.80 +/- 0.16 nM (100 ng/min/kg). Extending the infusion period of LTB4 up to 330 min did not result in an enhanced inhibition of the neutropenia in response to bolus injections of LTB4. Reversibility of the desensitization was shown by an almost complete recovery of the neutropenic response within 30 min after cessation of the infusion. The desensitization achieved towards LTB4 showed some specificity, inasmuch as a profound and reversible neutropenia was observed in response to a bolus of either FMLP or C5a under conditions in which sensitivity to LTB4 was lost. These findings suggest that a specific desensitization to LTB4 is feasible in vivo and may constitute a useful approach, in addition to the use of 5-lipoxygenase inhibitors and LTB4 antagonists, to delineate the significance of LTB4 as a mediator of inflammation.
Animals↗
Treatment of diabetic ketoacidosis in dogs by continuous low-dose intravenous infusion of insulin.
In a prospective clinical trial, low-dose, continuous, IV infusion of insulin (dosage, 2.2 U/kg of body weight, q 24 h) was used to treat 21 dogs with diabetic ketoacidosis. Mean (+/- SD) blood glucose concentration at the onset of treatment was 550 +/- 150 mg/dl and after 6 hours, was 350 +/- 106 mg/dl, with a mean decline of 34 +/- 16 mg/dl/h. By 12 hours, mean blood glucose was 246 +/- 85 mg/dl, with a mean decline of 28 +/- 14 mg/dl/h during the second 6 hours of treatment. Mean duration of treatment required to reach a blood glucose concentration < or = 250 mg/dl was 10 +/- 4 hours, with a range of 4 to 24 hours. Ketonuria was observed for 26 +/- 14 hours (range, 6 to 72 hours). Hypoglycemia developed in 3 of 21 dogs during treatment, but responded to IV administration of a glucose solution and to a reduction in rate of insulin delivery. Potassium supplementation was required in 15 of 21 dogs. Mean bicarbonate concentration was 11.6 +/- 3.4 mEq/L before treatment and was 18.2 +/- 0.7 mEq/L after 24 hours. Fifteen of 21 dogs (71%) survived to be discharged. Mean duration of treatment with the insulin infusion was 50 +/- 30 hours (range, 7 to 124 hours). In this series of dogs, continuous, low-dose, IV infusion of insulin provided a gradual and consistent reduction in blood glucose concentration while ketoacidosis, electrolyte balance, and dehydration were corrected.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗
A phase I-II trial of five-day continuous intravenous infusion of 5-fluorouracil delivered at circadian rhythm modulated rate in patients with metastatic colorectal cancer.
The toxicity of 5-fluorouracil (5-FU) was decreased by two to eight-fold if this drug was injected in mice near the middle of the day (rest span) rather than in the middle of the night (activity span). If the rhythm in 5-FU toxicity is linked to the sleep-wakefulness endogenous circadian cycle across species, the least toxic time in man would correspond to 4.00 hours at night. The availability of a single-reservoir programmable-in-time external ambulatory pump (Chronopump, Autosyringe, Hooksett, USA) allowed us to perform a first test of this hypothesis. Five-FU was infused for 5 consecutive days, via an implanted venous access port, with peak drug delivery at 4.00 hours and no infusion from 18.00 to 22.00 hours. Each course was repeated after a free interval of 16 days. Intrapatient dose escalation was planned from 4 to 9 g/m2/course (800 to 1800 mg/m2/day x 5 days) if toxicity was less than grade 2 according to the World Health Organization (W.H.O.). Thirty-five patients with metastatic colorectal cancer were treated; 15 (41%) had received previous therapy, 22 (63%) had W.H.O. performance status of 2 or greater, and 19 (54%) had two or more sites involved. Grade 2 or greater toxicity was encountered in less than 5% of the courses, indicating an adequate control of toxicity via dose adjustment. Oral mucositis, diarrhea, and/or hand-foot syndrome limited dose escalation, and their incidence was dose dependent. Median maximal tolerated dose was 7.5 mg/m2/course in 30 patients assessed for this endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pharmacokinetics and metabolic pattern after intravenous infusion and oral administration to healthy subjects.
Meloxicam [4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H- 1,2-benzothiazine-3-carboxamide-1,1-dioxide] is a new nonsteroidal antiinflammatory drug belonging to the enolic acid group. In a crossover study, 30 mg 14C-labeled meloxicam was administered to four male healthy volunteers as a short-term infusion and as an oral solution. The objectives of the study were to determine the mode of elimination, the excretion balance, the in vivo binding characteristics to serum proteins, and to investigate the metabolic pattern in plasma, urine, and feces. A comparison of plasma concentration measurements of unchanged drug by a specific HPLC assay and total radioactivity by liquid scintillation counting revealed a very close conformity. Over 90% of the plasma radioactivity was represented by unchanged drug. Its terminal and dominant half-life of elimination from plasma, as determined from plasma and urinary data in this study, ranged from 12 to 17 hr in the volunteers. The serum protein binding of the radioactivity from in vivo samples was very high (99.1-99.7%). The excretion balance was complete after 6 days. Average urinary excretion of 14C-radioactivity accounted for 43% of the dose, with the remainder appearing with the feces. Meloxicam was extensively metabolized, with only traces of the drug appearing unchanged in urine and feces. The main metabolites were formed by hydroxylation and further oxidation of the methyl group of the thiazolyl moiety. In addition, two further metabolites were found, particularly in urine. Altogether, > 95% of the dose excreted could be accounted for by the metabolites identified or the parent compound itself.
Administration, Oral↗
[99mTc-MIBI myocardial tomography with intravenous infusion of adenosine triphosphate in the diagnosis of coronary artery disease].
To evaluate its feasibility, safety and diagnostic accuracy, 99mTc-MIBI myocardial tomography with adenosine triphosphate (ATP) infusion (0.16 mg/kg/min for 5 min) was performed 100 consecutive patients using the stress/rest one day protocol. None of the patients required treatment with aminophylline during the study. The sensitivity and specificity for detecting patients with coronary artery disease were 97% and 71%, respectively. Those for detecting individual coronary lesion (> or = 75% stenosis) were 92% and 89%, respectively. The high hepatic uptake of 99mTc-MIBI causes artifactual perfusion defects in the inferior myocardial wall, particularly on ATP stress images. In order to reduce this artifactual phenomenon, the interval time between injection and stress imaging must be increased.
Adenosine Triphosphate↗
Phase I study of high-dose continuous intravenous infusion of VP-16 in combination with high-dose melphalan followed by autologous bone marrow transplantation in children with stage IV neuroblastoma.
The purpose of the study was to determine the maximum tolerated dose of continuous infusion of high-dose VP-16 in combination with high-dose melphalan (HDM) for conditioning before autologous bone marrow transplantation (ABMT). Thirteen children (median age 27 months) with stage IV neuroblastoma were treated with high-dose VP-16 and HDM followed by ABMT as consolidation treatment. All had previously received conventional chemotherapy with a mean number of six drugs. Surgery of the primary tumor had been performed in 12/13. We performed a dose-escalating study of VP-16 from 1800 mg/m2/72 h with 300 mg/m2/72 h dose increments according to toxicity. VP-16 was administered as a 72-h i.v. infusion. Melphalan (140 mg/m2/day) was administered once as an i.v. push. VP-16 pharmacokinetics were analyzed in 12 patients. Five children received 1800 mg/m2/72 h of VP-16, five received 2100 mg/m2/72 h and three, 2400 mg/m2/72 h. The mean duration of granulocytopenia (< 0.5 x 10(9)/1) was 24 days and thrombocytopenia (< 50 x 10(9)/1) was 36 days. No major infectious complications occurred. Gastrointestinal (GI) toxicity was the dose-limiting toxicity. Five severe manifestations of GI toxicity in three patients led us to consider 2400 mg/m2/72 h as the MTD. The mean VP-16 clearance rate was 17.3 ml/min/m2 with continuous infusion. A mean steady-state plasma concentration of 24.2 micrograms/ml (s.d. = 2) and 28.3 micrograms/ml (s.d. = 1.9) was achieved at the 1800 mg/ml and 2100 mg/m2 dose levels, respectively, GI toxicity is dose limiting when VP-16 at 2400 mg/m2/72 h, is associated with HDM. When given as a continuous i.v. infusion, at 2100 mg/m2/72 h, VP-16 associated with HDM is well tolerated before ABMT in young heavily pre-treated children.
Antineoplastic Combined Chemotherapy Protocols↗
Interdisciplinary development of an intravenous infusion protocol for Orthoclone OKT3.
The development and implementation of an infusion protocol for Orthoclone OKT3 (Ortho Biotech, Inc., Raritan, NJ) is described in this article. OKT3 is a potent immunosuppressant drug used to lower the incidence of graft rejection in transplant patients. Nurses and physicians use the protocol described in this article to administer OKT3 to heart and lung transplant patients at our institution. Pharmacokinetics, along with the nursing care, associated with OKT3 administration are described in the protocol section. The benefits of protocol use are reported in the conclusion.
Humans↗
Anthracycline dose intensity: clinical pharmacology and pharmacokinetics of high-dose doxorubicin administered as a 96-hour continuous intravenous infusion.
In this review, the clinical pharmacology of high-dose doxorubicin is examined, and the pharmacokinetics of infusional doxorubicin at standard and high dose are compared. The data developed here, including recent clinical trials of high-dose infusional doxorubicin, demonstrate the safety and efficacy of doxorubicin administration at doses > or = 150 mg/m2 for patients with breast cancer and strongly suggest that the utility of this drug can be substantially increased with appropriate hematopoietic support.
Antibiotics, Antineoplastic↗