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[Phlebitis due to intravenous administration of macrolide antibiotics. A comparative study of erythromycin versus clarithromycin].

BACKGROUND: To know and to compare the incidence of phlebitis due to intravenous administration of macrolide antibiotics erythromycin and clarithromycin. PATIENTS AND METHOD: Non-randomized prospective study of consecutive patients who were diagnosed of community pneumonia and treated with intravenous macrolides (19 with erythromycin and 25 with clarithromycin). RESULTS: The cumulative incidence of phlebitis in patients treated with erythromycin was 78.9% (incidence rate of 0.40 episodes/patient-day) and in those treated with clarithromycin 76% (incidence rate of 0.35 episodes/patient-day). CONCLUSIONS: The risk of phlebitis is high and similar with intravenous administration of both macrolides.

Anti-Bacterial Agents↗

Acute bone marrow aplasia associated with intravenous administration of deferoxamine (desferrioxamine).

The authors report the clinical course and fatal outcome of a case of acute bone marrow aplasia, after intravenous administration of deferoxamine (desferrioxamine) to a 16-year-old girl with homozygous beta-thalassaemia. The type of aplasia was mainly that of a megakaryocytic thrombocytopenia, but the 2 other haemopoetic series were also involved. The absence of any other toxic factors and the quite rapid onset of the bone marrow failure after this type of treatment strongly suggest that intravenous administration of high doses of deferoxamine was the potential toxic factor.

Adolescent↗

Protective effect of the intravenous administration of ursodeoxycholic acid against endotoxemia in rats with obstructive jaundice.

This study was undertaken to elucidate the effect of the intravenous administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with obstructive jaundice from the viewpoint of the biliary excretion of lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice, fluorescein isothiocyanate-labeled LPS was administered via the portal vein and then its biliary excretion was examined. A significant increase in the LPS excretion was thus noticed in UDCA-treated rats at a dose of 0.1 micromol/100 g body wt. per min. In place of UDCA, sodium taurocholate at the same dose also enhanced the biliary excretion of LPS. Secondly, we also examined whether or not UDCA protects against endotoxemia. In this experiment, nonlabeled LPS was administered via the portal vein and its peripheral concentration was then measured. In UDCA-treated rats, the endotoxin concentration was significantly lower. Finally, to elucidate the effect of UDCA on Kupffer cells, serum tumor necrosis factor (TNF-alpha) was measured. But UDCA had no effect on the TNF-alpha level. These findings thus demonstrate that the intravenous administration of UDCA protects against endotoxemia by enhancing the transport of LPS across the hepatocytes from blood to bile without affecting Kupffer cells, and that this biliary excretion of LPS is dependent on bile acids.

Analysis of Variance↗

Pharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in mice.

The pharmacokinetics and tissue distribution of Gentiopicroside (GPS), one of the major active components of the Gentiana species of medicinal plants, was studied following oral and intravenous administration in mice. The distribution of GPS in mice after oral and intravenous doses could be fitted to a two-compartments open model. The serum half-life of GPS was 6.1 h and 2.8 h for intravenous and oral administration, respectively. The Tmax of GPS after oral administration was 0.50 h, and the bioavailability was 39.6%. The AUC gradient in individual tissues following intravenous administration was kidney >serum >liver >spleen >lung >thymus >fat >heart >muscle >stomach >intestinal >brain. The MRT gradient was muscle >serum >lung >spleen >lung >intestinal>heart >stomach >brain >liver >thymus >kidney >fat. Overall the data show that GPS could be absorbed rapidly in mice, but with a low bioavailability, and could distribute to tissues extensively, but was generally cleared quickly with short MRTs. The study demonstrates the need for repeated dosage, or better, a slow release formulation as an ideal means of administering GPS.

Administration, Oral↗

Paradoxical excitement following the intravenous administration of azaperone in the horse.

The rapid intravenous administration of the butyrophenone tranquilliser, azaperone, at a dose rate of 0.29-0.57 mg/kg body weight resulted in the immediate onset of excitement and ataxia of varying degree in over half the animals. The severity of the reaction appeared to be related to the size of the animal. Other side effects such as salivation, sweating, muscle tremor and vocalisation were also observed. The possible causes of this paradoxical reaction to the tranquilliser are discussed.

Animals↗

Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemia-reperfusion rats after intravenous administration of Paeoniae Radix extract.

The time course of paeoniflorin in the cortex of normal and cerebral ischemia-reperfusion rats, following intravenous administration of Paeoniae Radix extract at a dose of 60 mg/kg of paeoniflorin, was determined using high-performance liquid chromatographic (HPLC) assay. The results showed that paeoniflorin could penetrate through the blood-brain barrier to reach the cortex, and that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin in the cortex after intravenous administration of Paeoniae Radix extract. The cortex concentrations of paeoniflorin in cerebral ischemia-reperfusion rats were lower 5 min after dosing and declined more slowly than that in normal control.

Animals↗

MRI visualization of proteoglycan depletion in articular cartilage via intravenous administration of Gd-DTPA.

The effect of intravenous administration of gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA) on MR images was studied in vitro, using pathologic osteochondral specimens removed during surgery for total endoprosthesis, and in vivo, on a group of volunteers. In ex vivo specimens, lesions of different shape having lower T1 were detected which corresponded to areas with depleted proteoglycans found histologically. In vivo experiments on young volunteers showed that the time course of cartilage enhancement was different for different anatomies. The time for maximum enhancement ranged from 45 min for the ventral femoral condyle to 270 min for patellar cartilage.

Adult↗

A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats.

The primary objective of this study was to test the hypothesis that intravenous administration of autologous bone marrow cells could improve functional recovery after middle cerebral artery occlusion (MCAO) for 45 min in the rat and to determine specific time windows for efficacy. Mononuclear cells from autologous bone marrow were transfected with the LacZ reporter gene, and injected intravenously into rats at 3-72 h after induction of MCAO. Histological analysis of the ischemic lesion at 14 days after transplantation revealed reduced ischemic lesion volume. Lesion volume was 250+/-45 mm(3) (n=6) after MCAO without cell transplantation. Lesions were minimally detected by absence of 2,3,5-triphenyltetrazolium chloride (TTC) staining when bone marrow cells were infused 3 h after lesion induction. Lesions were clearly detected beginning with the 6-h postlesion group and became progressively larger at 12, 24 and 72 h (80+/-25, 140+/-18, and 180+/-22 mm(3), respectively; n=6 for each group). Transplanted LacZ(+) bone marrow cells accumulated extensively in and around the ischemic lesions, and immunohistochemistry suggests some neuronal and glial lineage differentiation. Behavioral testing (Morris water maze and Treadmill stress test) indicated greater functional recovery in the treated group. These findings suggest that early intervention with intravenous administration of autologous mononuclear cells from bone marrow can reduce lesion size in the MCAO model in the rat, and improve functional outcome.

Animals↗

Captopril therapy in severe hypertension: effects of intravenous administration.

In 10 severe hypertensives the effects of intravenous administration of scalar doses of captopril were evaluated. The behaviour of blood pressure, heart rate, electrocardiographic pattern and left ventricular (LV) diastolic function, in basal condition (T0) and after 60 min of captopril infusion (T60), were analysed. Diastolic performance was assessed by pulsed wave Doppler echocardiography, evaluating transmitral peak flow velocities in early diastole (PEDV), late diastole (PLDV) and the PEDV/PLDV ratio. All patients showed an increase in LV mass (assessed by M-mode echocardiography) and altered diastolic performance, documented by high PLDV and low PLDV/PEDV ratio values. Clinical, haematological, urinary and biochemical data were also assessed for possible side effects. Captopril significantly reduced BP in 7 out of the 10 patients. Supine BP decreased from 212 +/- 15.3/126 +/- 5.6 to 171 +/- 17.7/98 +/- 11.8 mmHg (T0 vs. T60 P less than 0.0001). No electrocardiographic abnormality was observed during the study. The goal of antihypertensive effect was reached at 40-50 min after the onset of captopril therapy. Heart rate showed a small but constant decrease (from 76 +/- 7.7 to 72.8 +/- 5.7 beats/min, T0 vs. T60, P less than 0.05). Side effects of intravenous captopril were always mild and transient; no severe hypotension as 'first dose effect' was observed in our study. The echocardiographic data showed a significant decrease in LV end-systolic dimension after captopril infusion, while left atrial, LV diastolic dimension and fractional shortening remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical study of sodium dicloxacillin for intravenous administration in heart surgery patients].

Sodium dicloxacillin for intravenous administration manufactured in the USSR was studied clinically in 21 cardiosurgical patients. The patients were operated with the use of artificial circulation. 16 patients received the drug for counteracting purulent inflammatory complications during the postoperative period. 5 septic patients were treated with dicloxacillin with curative purposes. The antibiotic proved to be highly effective in treatment and prevention of postoperative purulent complications in patients subjected to open-heart operations. 80 per cent of the Gram-stained isolates were sensitive to dicloxacillin. No pronounced complications with respect to the liver were observed in the patients treated with dicloxacillin.

Adolescent↗

Intratracheal administration of perfluorochemical-gentamicin suspension: a comparison to intravenous administration in normal and injured lungs.

Respiratory infections can lead to acute lung injury and perfusion abnormalities. We hypothesized that intratracheal (IT) administration of a perfluorochemical (PFC) gentamicin (G) suspension as compared to intravenous (IV) administration of gentamicin will result in higher lung tissue levels of gentamicin, while maintaining safe serum levels. To test this hypothesis, 21 lambs with normal and acid injured lungs were studied for 4 hr, using 2 different drug delivery methods, IT and IV. Lungs were injured with warm HCl acid in saline lavage, followed by partial liquid ventilation with perflubron (bolus FRC = 20 mL/kg). G at a dose of 5 mg/kg was delivered either IT (G-PFC; 20 mL/kg) or IV (aqueous injection with IT 20 mL/kg PFC alone). Throughout the study, serum G levels, arterial blood gases, respiratory system compliance, and mean arterial blood pressure were measured. Lung tissue G levels were measured at 4 hr and averaged across lobes. Physiologic gas exchange and pulmonary function were maintained throughout the protocol for both the normal and injured lungs. Intravenously administered G resulted in an initial 5-min serum concentration of 43 +/- 2.5 mcg/mL, followed by an exponential decline over the 4-hr protocol to a level of 2.1 +/- 0.23 mcg/mL at hr 4. The intratracheally administered G suspension resulted in a 5-min serum concentration of 1.8 +/- 0.98 mcg/mL and remained relatively constant throughout the protocol, with a 4-hr level of 1.6 +/- 0.29 mcg/mL. With respect to lung tissue G levels, IT administration was significantly more effective in delivering the drug to the normal lungs than IV (31.4 +/- 3.3 mcg/g vs. 4.0 +/- 0.7 mcg/g) 4 hr after administration. In the lung injury group, there was a small but significant difference in lung tissue G levels, with the IT-administered perfluorochemical-G suspension achieving greater levels than the IV-administered G (11.9 +/- 0.52 mcg/g vs. 10.1 +/- 0.8 mcg/g). Additionally, the drug delivered IV and IT in both the normal and injured lung models was homogeneously distributed throughout the lung. These data show that G lung tissue levels in both normal and injured lungs were higher in the IT group when compared to IV administration. The results of this study demonstrate that in normal and injured lungs, homogeneous G lung tissue levels can be more effectively achieved at lower serum levels when delivered IT in a G-PFC suspension as compared to IV administration.

Animals↗

[Early ultrastructural lesions of kidney cells after intravenous administration of 239 plutonium citrate in rats].

After intravenous administration of (5 x 2.3 kBq and 5 x 9.25 kBq) plutonium citrate in adult male Sprague Dawley rats, their kidneys are withdrawn and prepared for observation under a transmission electron microscope. Seven days after the first injections, deep cellular alterations are observed in the proximal convoluted tubules. These alterations are mainly mitochondrial. The affected mitochondria are of swollen aspect and have their cristae partially or completely destroyed. Nevertheless within the same tubule we observe non altered cells directly in contact with deeply altered cells. In all the cases the lysosomes of the altered cells appear to be perfectly normal. The cell nuclei are mostly unaltered but a few cases of nuclear fragmentation exist. We also notice some architectural modifications in the brush border and in the betacytomembranes of the proximal convoluted tubule. Equally important mitochondrial alterations are also noticed in the different varieties of glomerular cells. We observe no other glomerular alterations. The major subcellular alterations in the proximal convoluted tubules and in the different varieties of glomerular cells deeply contrast with the distal convoluted tubules which are found to be totally unaltered. These mitochondrial alterations may be due to the alpha particle disintegration of plutonium which may either directly react with the mitochondria or, through the products of radiolysis of water react with the mitochondria respiration process. However the direct chemotoxicity of plutonium cannot be neglected.

Animals↗

Effects of intravenous administration of slow-reacting substance of anaphylaxis, histamine, bradykinin, and prostaglandin F2alpha on pulmonary mechanics in the guinea pig.

The effects of intravenous administration of a purified preparation of slow-reacting substance of anaphylaxis (SRS-A), histamine, bradykinin, and prostaglandin F(2alpha) (PGF(2alpha)) on the mechanics of respiration were assessed in the unanesthetized guinea pig. Geometrically increasing doses of SRS-A resulted in graded decreases in average pulmonary compliance, with only modest increases in average pulmonary resistance. A dose with apparent maximal effects. 3,000 U/kg, resulted in a decrease of 49+/-7% of compliance below control values, with an increase in resistance of 24+/-8% above control. Intravenous administration of geometrically increasing amounts of histamine, bradykinin, and prostaglandin F(2alpha) also resulted in decreased compliance; but in each case this was accompanied by a marked increase in respiratory resistance. A decrease of compliance of approximately 50%, induced by intravenous histamine, bradykinin, or PGF(2alpha), was accompanied by an increase of 60-140% in resistance. Thus, intravenously administered SRS-A alters pulmonary mechanics with a more peripheral effect than any of the other agents tested.

Airway Resistance↗

Pharmacokinetic studies of 5-fluorouracil after oral and intravenous administration in man.

The pharmacokinetic conditions for oral administration of 5-fluorouracil (5-FU) were investigated in 16 patients with malignant liver tumours. The concentration of 5-FU in portal and systemic blood was determined by a microbiologic method every 10 min. during 2 hours after oral or intravenous administration of a standard dose of 250 mg 5-FU ( approximately 4 mg/kg b. wt.) or 15 mg 5-FU/kg b. wt. The drug was rapidly absorbed after oral administration with peak values within 10-30 min. 25% of the lower and 40% of the higher oral dose reached the systemic circulation. The reduction of systemic bio-availability was partly accomplished by a loss in the gastrointestinal tract and partly by extraction by the liver. The hepatic extraction ratio was calculated to 0.56 and 0.26 after the lower and the higher dose respectively indicating a saturable process. The availability of 5-FU was significantly higher in portal blood than in systemic blood after oral administration. The opposite conditions were found after intravenous administration. Thus, oral administration of 5-FU to patients with malignant liver tumours seems rational.

Administration, Oral↗

Pharmacokinetics of etodolac in the horse following oral and intravenous administration.

The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two-way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half-life (t(1/2)) of 2.67 h, volume of distribution (Vd) of 0.29 L/kg and clearance (Cl) of 234.87 mL/h kg. Following oral administration, the average maximum plasma concentration (Cmax)) was 32.57 mug/mL with a t(1/2) of 3.02 h. Bioavailability was approximately 77.02%. Results of in vitro COX selectivity assays showed that etodolac was only slightly selective for COX-2 with a COX-1/COX-2 selectivity ratio effective concentration (EC)50 of 4.32 and for EC80 of 4.77. This study showed that etodolac is well absorbed in the horse after oral administration, and may offer a useful alternative for anti-inflammatory treatment of various conditions in the horse.

Administration, Oral↗

[Effect of metoprolol on the circulation after head trauma. Studies during continuous intravenous administration (author's transl)].

The influence of continuous intravenous administration of metoprolol on heart rate and haemodynamics was tested in ten unconscious patients who, after sustaining a head injury, developed sinus tachycardia due to increased sympathicotonia. In preliminary studies on three patients the effective dosage for heart rate reduction was determined. Following this, seven patients received 0.15 mg/kg . h of metoprolol over 36 hours. Heart rate decreased from an average of 127.5 to 78.8/min, a statistically significant reduction. Stroke volume index significantly rose from an average of 35.5 to 52.3 ml/m2, while other haemodynamic variables were not or only slightly changed. Cardiac index fell (not significantly) from 4.51 to 3.81/min . m2, peripheral vascular resistance rose (not significantly) form 942.4 to 1061.7 dyn . s . cm-5. Arterial and pulmonary artery pressures as well as filling pressures of right and left ventricle and left ventricular work index were not altered. Total oxygen consumption and oxygen extraction rate also remained unchanged. Measurement of metoprolol plasma levels in four patients excluded the possibility of a cumulative effect.

Adult↗

Anaphylactic bronchoconstriction in immunized guinea pigs provoked by inhalation and intravenous administration of hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride.

We established a guinea-pig model of anaphylactic bronchoconstriction provoked in immunized animals by inhalation and intravenous administration of 4,4-methyltetrahydrophthalic anhydride (MTHPA) and hexahydrophthalic anhydride (HHPA). Guinea pigs were immunized intradermally with either MTHPA (n = 8) or HHPA (n = 8) suspended in olive oil. Control animals (n = 8) were injected with olive oil alone. After 4 weeks, the animals were challenged during mechanical ventilation by inhalation or intravenous administration of MTHPA or HHPA conjugated with guinea-pig serum albumin (GPSA). Airway flow, and airway and esophageal pressures were measured. Resistance (R) and static compliance (Cst) of the respiratory system (rs), lung (1), and chest wall were studied with the flow-interruption technique. After challenge with MTHPA-GPSA or HHPA-GPSA, R,rs and R,1 increased dramatically while Cst,rs and Cst,1 decreased, and severe arterial hypoxia developed. The reaction occurred at a well-defined dose of anhydride and lasted about 30 min. When the same dose was repeated after 30 min, the response was much attenuated. MTHPA and HHPA can induce asthma in guinea pigs. The dose-response curve at antigen challenge is steep. Once a threshold dose is reached, a severe reaction occurs. The reactivity is then exhausted. This model may be suitable for assessing occupational asthma caused by acid anhydrides and possibly by other low-molecular-weight chemicals.

Administration, Inhalation↗

Oral versus intravenous administration of butylbiguanide: effect on oral glucose tolerance in normal humans.

1. The effect of oral and intravenous administration of butylbiguanide on the oral glucose tolerance test was investigated in 12 normal human volunteers. Orally administered butylbiguanide lowered the oral glucose tolerance curve and the corresponding serum insulin values, whereas intravenously injected butylbiguanide had no effect. 2. The lactate/pyruvate ratio determined 180 min. after glucose ingestion increased after oral butylbiguanide administration. No effect was observed after intravenous administration. 3. The decrease in serum phosphate levels observed after oral glucose loading was not influenced by butylbiguanide administered by either route. In addition, no effect of this drug was observed on fasting levels of glucose, insulin, phosphate, bicarbonate, lactate and pyruvate. 4. These results are compatible with recent observations that biguanides inhibit active transport mechanisms in the intestine. In addition, the effect of biguanides on blood levels of glucose metabolites is discussed with respect to their known action on oxidative phosphorylation.

Administration, Oral↗