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PubMed1994

Systemic and renal effect of intravenous infusion of endothelin-1 in healthy human volunteers.

The effect of intravenous infusion of endothelin-1 (ET-1) at a rate of 1 pmol.min-1.kg-1 for 60 min (n = 9) or placebo (n = 9) was investigated in 18 healthy human volunteers with a mean age of 30 yr. In response to ET-1 infusion, concentration of ET-1 increased from 0.88 +/- 0.27 to 10.73 +/- 4.79 (SD) pmol/l. Diastolic blood pressure increased by 7.8% (P < 0.01) and heart rate decreased by 14.0% (P < 0.01), whereas systolic blood pressure did not change. Renal plasma flow decreased by 34.7%, glomerular filtration rate decreased by 16.1%, and renal vascular resistance increased by 66.0% (P < 0.01 all). Urinary sodium excretion decreased by 57.9% and urinary flow rate by 40.2% (P < 0.01 for both). As judged from the clearance of lithium, we found that ET-1 did not change absolute reabsorption of sodium and water in the proximal tubules, but in the distal tubules absolute reabsorption of both sodium and water decreased significantly. Plasma concentrations of angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide did not change in response to ET-1 infusion. It is suggested that ET-1 at plasma concentrations found in certain pathophysiological conditions in humans may influence renal perfusion and renal sodium and water excretion.

Adult↗
PubMed1994

Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects.

In a single-blind, randomized, two-way cross-over study with 12 healthy male volunteers, 60 micrograms of prostaglandin E1 (PGE1) or placebo was administered by intravenous infusion during a 120-min period. PGE1, 13,14-dihydro-PGE1 (PGE0) and 15-keto-PGE0 plasma concentrations were measured by a highly specific and sensitive GC-MS/MS method. Endogenous PGE1 plasma concentrations ranged between 1.2 and 1.8 pg.ml-1. Endogenous PGE0 and 15-keto-PGE0 plasma concentrations varied from 0.8 to 1.3 pg.ml-1 and from 4.2 to 6.0 pg/ml respectively. During intravenous infusion of PGE1, plasma PGE1 concentrations rose to a level twice as high as during the placebo infusion. In contrast, PGE0 plasma concentrations were 8 times higher during PGE1 infusion than during placebo infusion, and 15-keto-PGE0 plasma concentrations were 20 times higher. The new analytical method has thus been useful to describe the pharmacokinetics of PGE1 and its metabolites PGE0 and 15-keto-PGE0, during and after intravenous infusion of PGE1.

Adult↗
PubMed1992

Efficacy of cilofungin therapy administered by continuous intravenous infusion for experimental disseminated candidiasis in rabbits.

Cilofungin has potent in vitro activity against Candida albicans, but previous in vivo models using twice daily intermittent dosing regimens have not consistently demonstrated in vivo efficacy. Because of the pharmacokinetics of cilofungin in rabbits, it has been suggested that administration by continuous intravenous infusion might be more effective. We compared the in vivo efficacy of continuous intravenous infusion of cilofungin with that of amphotericin B in a rabbit model of disseminated candidiasis. Cilofungin prepared as previously described in phosphate-buffered 33% polyethylene glycol was lethal to infected rabbits in this model, as was phosphate-buffered 33% polyethylene glycol alone. In contrast, cilofungin in 26% polyethylene glycol and sterile water administered by continuous intravenous infusion was tolerated by rabbits, was significantly more effective than amphotericin therapy in reducing candida colony counts in kidney tissue, and was as effective as amphotericin therapy in lung and spleen tissue and in cardiac valvular vegetations. The dosage regimen and diluent used in some previous studies may have adversely affected outcome of treatment with cilofungin.

Amphotericin B↗
PubMed1996

[Study on clinical effect of a continuous intravenous infusion of azasetron against nausea and vomiting induced by anticancer drugs including CDDP].

Azasetron, a selective 5-HT3 receptor antagonist, has been previously shown to be highly effective in the prophylaxis of nausea and vomiting induced by anticancer drugs and is widely used in the clinical setting in Japan. In order to improve the antiemetic effect of azasetron, we designed a continuous intravenous infusion method of this drug and compared the antiemetic effect of this method with that of standard bolus intravenous injection on nausea and vomiting associated with anticancer drugs including 75 mg/m2 cisplatin (CDDP). A continuous group is intravenous bolus injection of 2.5 mg azasetron followed by 7.5 mg continuous intravenous infusion for 24 hrs, and a bolus group is intravenous bolus injection of 10 mg azasetron. The inhibitory effect on nausea of the continuous group was significantly superior to those of the bolus group on day 3 and 4 (p < 0.05) and inhibitory effect on vomiting of the continuous group was significantly superior to those of bolus group on day 2 (p < 0.05). No adverse effects were observed in either group of this study. From these data, continuous intravenous infusion of azasetron was considered to be highly effective in prophylaxis of nausea and vomiting induced by anticancer drugs.

Adult↗
PubMed1988

The metabolism of prostaglandin D2 after inhalation or intravenous infusion in normal men.

Tritium-labelled prostaglandin D2 (PGD2) was administered to normal volunteers by either intravenous infusion or inhalation in order to establish which metabolites of PGD2 are initially found in human plasma. Inhaled PGD2 was rapidly absorbed from the airways, as indicated by the rapid appearance of tritium in the plasma. Metabolites chromatographically similar to 9 alpha,11 beta-PGF2 and 13,14-dihydro-15-keto-9 alpha,11 beta-PGF2 were found after both routes of administration. At later time points, other unidentified compounds were present. Only after intravenous infusion was there evidence of metabolites with 9 alpha,11 alpha stereochemistry of the ring hydroxyl functions. In human lung, 9 alpha,11 beta-PGF2 was metabolized in the presence of NAD+ to compounds tentatively identified by gas chromatography/mass spectrometry (GC/MS) as 15-keto-9 alpha,11 beta-PGF2 and 13,14-dihydro-15-keto-9 alpha,11 beta-PGF2. Thus, after 11-ketoreductase-dependent metabolism of PGD2 to the biologically active compound 9 alpha,11 beta-PGF2, further metabolism probably proceeds by the combined action of 15-hydroxyprostaglandin dehydrogenase/15-ketoprostaglandin-delta 13-reductase (15-PGDH/delta 13R). Both 9 alpha,11 beta-PGF2 and its 13,14-dihydro-15-keto metabolite may be useful analytes for the measurement of PGD2 turnover, and may therefore prove to be important in understanding the pathophysiological significance of this putative mediator.

Administration, Inhalation↗
PubMed1998

[Effects of intravenous infusion of 5-FU and intraperitoneal injection of low-dose CDDP on 3 cases with ascites owing to peritonitis carcinomatosa of postoperative gastric carcinoma and debility].

We examined the effects of intravenous infusion of 5-FU and intraperitoneal injection of low-dose CDDP on 3 cases with ascites owing to peritonitis carcinomatosa of postoperative gastric carcinoma and debility. Intravenous infusion of 5-FU (250-1,000 mg/body) and intraperitoneal injection of CDDP (20-25 mg/body) carried out for 2-5 days. As a result, QOL of 3 cases was fairly improved. The PS (Performance Status) of 2 cases improved from Grade 4 to 2, and another one improved from Grade 4 to 3. Adverse effects of Grade 1 according to the WHO criteria were observed in 1 case (leukocytopenia and diarrhea). This palliative chemotherapy method appeared to be safe and effective for ascites due to peritonitis carcinomatosa of postoperative gastric carcinoma and debility.

Aged↗
PubMed2001

Methyl-beta-cyclodextrin: an alternative carrier for intravenous infusion of palmitate during tracer studies in swine (Sus scrofa domestica).

Fatty acid-free albumin has been the standard carrier for intravenous infusion of fatty acids to study in vivo lipid metabolism. However, subjects can have adverse reactions to infusion of albumin. We sought an alternative to albumin as a carrier for intravenous infusion of fatty acids, using the pig as a model. Cyclodextrins are naturally occurring water-soluble molecules that can serve as carriers for lipid-soluble compounds. 13C-palmitate was complexed to either 20% methyl-beta-cyclodextrin, 20% 2-hydroxypropyl-beta-cyclodextrin, or 5% porcine albumin (isotopic purity of infusates: 99.22+/-0.06%). 13C-palmitate-albumin was infused under fed conditions and 13C-palmitate-methyl-beta-cyclodextrin was infused under fasted and fed conditions in 50-kg pigs. Palmitate remained in solution at 4 degrees C in methyl-beta-cyclodextrin, but precipitated at 25-30 degrees C in 2-hydroxypropyl-beta-cyclodextrin. Pigs infused with 13C-palmitate-methyl-beta-cyclodextrin maintained normal body temperature and appetite; those infused with 13C-palmitate-albumin became anorexic and exhibited other negative side effects to albumin. Palmitate oxidation rates under fed conditions were similar using either 13C-palmitate-methyl-beta-cyclodextrin or 13C-palmitate-albumin complexes. Fasting increased 13C-palmitate-methyl-beta-cyclodextrin oxidation by approximately eight-fold. These data suggest that methyl-beta-cyclodextrin may be a suitable substitute for albumin in fatty acid metabolism studies in swine.

Albumins↗
PubMed1994

Treatment of cancer-associated hypercalcemia. Double-blind comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone.

BACKGROUND: We assessed the effects of 60-mg single doses of pamidronate disodium compared with saline alone in the treatment of cancer-associated hypercalcemia. METHODS: After pretreatment hydration, patients with corrected serum calcium concentrations of 3.0 mmol/L (12 mg/dL) or greater secondary to cancer were randomized to double-blind treatment with a single infusion of pamidronate disodium, 60 mg, over either 4 or 24 hours or continued infusions of 0.9% saline alone (n = 23 per group). Corrected serum calcium levels were measured daily for 7 days of inpatient evaluation. RESULTS: Response rates for both of the pamidronate regimens were significantly (P < .05) higher than that for saline alone. A complete response to treatment (corrected serum calcium concentration normalized) was observed for five (22%), 18 (78%), and 14 (61%) patients, respectively, who received saline alone, 4-hour infusion of pamidronate, and 24-hour infusion of pamidronate. There were no significant differences between the two pamidronate regimens. Median durations of complete response were 6, 6, and 11 days, respectively, and median times to relapse (includes complete plus partial responders and nonresponders) were 0, 7, and 7 days, respectively. Pamidronate was well tolerated as assessed by all clinical and laboratory measures, regardless of the time of infusion. CONCLUSIONS: A 4-hour infusion of pamidronate disodium, 60 mg, was as safe and effective as a 24-hour infusion, and both were superior to saline alone in lowering corrected serum calcium concentrations in patients with cancer-associated hypercalcemia.

Adult↗
PubMed1989

Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma.

Two hundred and seventy-four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48-hour (79 patients) or 96-hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinical cardiac dysfunction developed. The complete remission rate was 21% the partial remission rate, 59%. There were no differences in response rate, response duration, or survival duration between groups of patients treated with doxorubicin by bolus, 48-hour or 96-hour infusion FAC. The incidence of moderate and severe nausea and vomiting was lower in the group of patients treated with infusion FAC as compared to bolus FAC (P less than 0.001); however, the incidence of mucositis was higher in the infusion group than in the bolus group (P less than 0.001). Doxorubicin administered by continuous infusion schedules was less cardiotoxic than when administered by bolus, as shown by a greater than 75% decrease in the frequency of clinical congestive heart failure at cumulative dosages greater than or equal to 450 mg/m2 (P = 0.004). Doxorubicin administered as a 48-hour or 96-hour continuous IV infusion is safer, and better tolerated than doxorubicin administered by bolus.

Adult↗
PubMed1989

A phase I study of thiotepa administered by short-term and protracted continuous intravenous infusion.

Forty-five patients received escalating dose rates of continuous infusion thio-triethylene thiophosphoramide (TEPA) for either five (26 patients) or 28 (19 patients) days. Dose rate limiting toxicity for the 5-day infusion was myelosuppression with leukocyte and platelet nadirs on days 21 and 28, respectively. The nadir was influenced by the presence and degree of liver disease. The optimal dose rate for 5-day infusion in the absence of liver disease was 12 mg/m2/d and was reduced to 8 mg/m2/d in patients with major liver disease. Dose rate limiting toxicity for the protracted 28-day infusion was leukopenia. The optimal dose rate for the 28-day infusion was 4 mg/m2/d. Pharmacologic studies included determination of plasma steady state concentrations (CSS) of thio-TEPA and TEPA. Dose rates up to 10 mg/m2/d produced thio-TEPA and TEPA CSS below the levels of detection of available analytical methodology, except in three patients infused at dose rates of 1, 2, and 4 mg/m2/d, respectively.

Adult↗
PubMed2000

Relationships between steady state blood concentrations and cardiac output during intravenous infusions.

The blood concentration of a drug at steady state can be calculated from the ratio of infusion rate over the total body drug clearance. When the blood is assumed to be a homogenous pool, the clearance is not usually referenced to any particular site within the circulation. In contrast, in recirculating systems, the relative sites of an infusion, the lungs and organs of elimination, and dilution in the cardiac output, produce concentration gradients in the blood. Equations that describe the relationship between the steady state concentrations of a drug in arterial, pulmonary artery, mixed venous and eliminating organ (e.g. liver or kidney) blood and the intrinsic clearance of the drug in the lungs and the eliminating organ were derived analytically. The concentrations at all sites were shown to be cardiac output dependent with the following exceptions: (1) in arterial blood, when the drug is highly extracted by the lungs, and (2) in eliminating organ blood when there is no lung clearance of the drug. The arterial and pulmonary artery concentrations will be least affected by cardiac output in the absence of lung clearance, and if the intrinsic clearance in the eliminating organ is substantially less than cardiac output.

Blood Circulation↗