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PubMed2004

Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury.

This study was designed to investigate the effects of intravenous administration of marrow stromal cells (MSCs) on the expression of growth factors in rat brain after traumatic brain injury (TBI). The fate of transplanted MSCs and expression of growth factors was examined by immunohistochemistry. In addition, the level of growth factors was measured quantitatively using enzyme linked immunosorbent assay (ELISA). Growth factors that were studied included nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). For immunohistochemical studies, 12 male Wistar rats were subjected to TBI and then divided into three groups with the first group receiving no treatment, the second group receiving saline (placebo) and the third group receiving MSCs intravenously 1 day after TBI. The neurological function of rats was studied by using Rotarod motor test and modified neurological severity scores. The animals were sacrificed 15 days after TBI and brain sections stained by immunohistochemistry to study the distribution of MSCs as well as expression of growth factors NGF, BDNF, and bFGF. For quantitative analysis, a second set of male Wistar rats (n = 18) was subjected to TBI and then injected with either saline (n = 9) or MSCs (n = 9) 1 day after injury. These rats were sacrificed on days 2, 5, and 8 after TBI and brain extracts used to measure NGF, BDNF, and bFGF. We found that after transplantation, MSCs preferentially migrated into the injured hemisphere and there was a statistically significant improvement in the functional outcome of MSC-treated rats compared to control rats. NGF, BDNF, and bFGF were expressed in the injured brain of both treated as well as control rats; however, quantitative ELISA studies showed that expression of NGF and BDNF was significantly increased (p < 0.05) in the treated group. This study shows that intravenous administration of MSCs after TBI increases the expression of growth factors (NGF, BDNF), which possibly contributes to the improvement in functional outcome seen in these rats.

Animals↗
PubMed1990

Comparison of 5-fluorouracil pharmacokinetics following intraperitoneal and intravenous administration using in vivo 19F magnetic resonance spectroscopy.

Intrahepatic pharmacokinetic studies of 5-Fluorouracil (5 FU) metabolism following intravenous and intraperitoneal administration have been undertaken in four patients using in vivo 19F nuclear magnetic resonance spectroscopy. Following intravenous administration, 5 FU decayed with "half times" ranging from 5 to 17 min. There was considerable variation of 5 FU pharmacokinetics between patients following intraperitoneal administration. Peritoneal contamination by infused 5 FU was considered to be a significant problem in one patient. A technique for providing superficial signal suppression was therefore investigated and its efficacy for excluding signal from the peritoneal space has been demonstrated. Owing to the potential for contamination from peritoneal 5 FU, the accumulation of fluoro-beta-alanine (FBAL) is a more reliable indicator of drug catabolism than the measurement of unlocalized "hepatic" 5 FU. Rapid intrahepatic catabolism of 5 FU to FBAL was demonstrated in all patients. However, there was greater pharmacokinetic variation following intraperitoneal administration than following intravenous administration. Therapeutic implications of intravenous compared with intraperitoneal administration of 5 FU are discussed.

Fluorouracil↗
PubMedDate not supplied

Use of trimethoprim-sulfamethoxazole in pediatric infections: relative merits of intravenous administration.

Trimethoprim-sulfamethoxazole (TMP-SMZ) has traditionally been employed as an oral formulation for infections in ambulatory pediatric patients. However, therapeutic concentrations of TMP and SMZ in serum and CSF are more consistently attained after intravenous administration. Serum half-life increases with the age of the child, and few significant toxic effects are observed with intravenous administration. Either the necessity to optimize bioavailability because of the underlying seriousness of disease or a desire to avoid other drugs that may be responsible for adverse reactions or hypersensitivity should direct the clinician to administer an intravenous preparation. Serious pediatric infections that might warrant the consideration of intravenous TMP-SMZ include shigellosis, salmonellosis, typhoid fever, nocardiosis, gram-negative bacillary septicemia or meningitis, and infections due to Pneumocystis carinii and malarial parasites. Infections due to Listeria will respond to TMP-SMZ, and infections due to Citrobacter diversus, Acinetobacter species, Pseudomonas cepacia, and Flavobacterium meningosepticum are especially susceptible to TMP-SMZ.

Age Factors↗
PubMed2006

Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat.

Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs) could contribute to functional recovery in a rat permanent middle cerebral artery occlusion (MCAO) model. We induced MCAO by using intraluminal vascular occlusion, and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited increased recovery from ischemia compared with the control group, but the effect was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber-mutant adenovirus vector may be useful in the cerebral ischemia and may represent a new strategy for the treatment of stroke.

Animals↗
PubMed1980

[Electrical standstill of the heart for 24 hours after intravenous administration of verapamil (author's transl)].

In a 47-year-old man suffering from sick-sinus syndrome the sinus node recovery time was determined. During rapid atrial stimulation a supraventricular tachycardia occurred. The intravenous administration of 10 mg Verapamil was followed by total electrical standstill of the heart lasting for more than 24 hours and requiring pacemaker therapy. This case demonstrates that the intravenous administration of Verapamil may be harmful.

Cardiac Pacing, Artificial↗
PubMed2006

Plasma profiles of lycopene after single oral and intravenous administrations in dogs.

The objectives of this study were to identify the factors limiting the absorption of purified lycopene after oral administration, and to comparatively assess plasma data sets after single oral and intravenous administrations in dogs to define the conditions for performing an absolute bioavailability study. Solubility of purified lycopene (all-trans, 93.5%) was determined in media simulating the conditions in the fasted and in the fed upper gastrointestinal lumen. After evaluating the plasma levels achieved following single administrations of purified lycopene powder to fasted and fed dogs at escalating doses (75-750 mg), a crossover study was performed in four fed female mongrel dogs at two phases. In phase I, one soft gelatine capsule (10 mg lycopene) with 500 mL milk was administered orally. In phase II, 500 mL milk was administered orally and 250 mL 5% dextrose containing 5 mg lycopene in the form of a binary system with hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was administered intravenously over 3.5 h. In-vitro and preliminary canine studies confirmed that, after oral administration of lycopene in solid form, arrival of lycopene into the systemic circulation was limited by lymphatic transport and, in addition, if the administered dose was higher than approximately 2 mg, by intralumenal solubility. During the first 50 h after single administrations to fed dogs, lycopene plasma levels were lower after intravenous than after oral administration. This could have been related to capacity limited elimination of lycopene and/or route-dependent disposition kinetics. Estimation of the amount of lycopene reaching the systemic circulation after oral and after intravenous administration requires separate estimations of total body clearance of lycopene.

Administration, Oral↗
PubMedDate not supplied

Metabolic studies in patients with nadolol: oral and intravenous administration.

Nadolol-14C, 2,3-cis-5-(3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol, a nonselective beta-adrenergic blocking agent, was administered orally and intravenously at 2-mg doses to patients with mild cases of essential hypertension. Terminal plasma half-times after oral and intravenous doses were an average of 12.2 and 9.8 hours, respectively. After oral doses, an average of 24.6 and 76.9 per cent of the dose was excreted in urine and feces, respectively, whereas, after intravenous doses, an average of 72.9 and 23.3 per cent of the dose was excreted by the same routes. Calculations of absorption, based on urinary excretion and on areas under the plasma concentration-versus-time curves, indicated that oral doses of nadolol-14C were absorbed to the extent of 33.6+/-2.4 per cent (+/- S.E.). The average overall volume of distribution after intravenous administration was 2.09+/-0.51 1./kg (+/- S.E.), and the average volume of the central compartment was 0.30+/-0.04 1./kg. Only unchanged nadolol-14C was excreted in the urine and feces of patients after either oral or intravenous administration of the drug.

Administration, Oral↗
PubMed1995

Cognitive and EEG recovery following bolus intravenous administration of anesthetic agents.

Bolus intravenous (IV) administration of commonly used IV anesthetic agents such as fentanyl and the fentanyl analogues, alfentanil, remifentanil, and sufentanil, etomidate and propofol, produced anesthesia in rats as measured by the loss of righting (LOR) with calculated ED150 doses of 0.06, 0.09, 0.037, 0.007, 2.51 and 6.12 mg/kg, respectively. Animals trained in an eight arm radial maze (RAM) were assessed for cognitive recovery, as measured by response efficiency (percentage of correct arm entries within 10 min), immediately, 15 min and 30 min following IV administration of the calculated ED150 dose of each of these agents, and the subsequent return of righting (ROR). Animals administered fentanyl or sufentanil were unable to successfully complete the maze throughout the testing periods. Animals receiving remifentanil showed cognitive recovery within the first testing interval (immediately following the return of righting), while animals receiving alfentanil, etomidate or propofol showed recovery at the 15-min testing interval following ROR. In a separate experiment, bolus IV administration of the ED150 dose of these agents was evaluated in an acute rat EEG model. Following ROR, return to baseline EEG levels occurred at 0.30, 2.88, 5.06, 16.25, 31.29 and 43.98 min for remifentanil, propofol, alfentanil, etomidate, fentanyl and sufentanil, respectively. These data show that the return to efficient cognitive functioning corresponds to the return to normal baseline EEG waveforms.

Alfentanil↗
PubMed1989

Kinetics of aluminum in rats I: Dose-dependent elimination from blood after intravenous administration.

Aluminum (Al) kinetics after intravenous bolus administration were studied in the rat. The animals received either 0.1 or 1.0 mg/kg (n = 6 at each dose) of elemental Al as the sulfate salt. The Al content of serial blood samples was determined by flameless atomic absorption spectrophotometry. Blood and plasma Al-time profiles after both doses were monoexponential in most cases. Increasing the administered dose increased the elimination half-life (mean +/- SD) from 1.20 +/- 0.25 to 2.41 +/- 0.26 h. A corresponding decrease in systemic clearance was observed (49.6 +/- 11.0 to 18.4 +/- 4.6 mL/kg.h). Both changes were significant (p less than 0.05). Significant differences were also observed in the volume of distribution, the values of which were 78.3 +/- 17.2 and 58.9 +/- 8.5 mL/kg at the low and high doses, respectively. At both doses, blood:plasma ratios ranged from 0.8 to 1.0, indicating considerable uptake/binding of the element by blood cells.

Aluminum↗
PubMed1987

[Complications and their elimination during the rapid intravenous administration of rifampicin in an experiment].

Reaction to rapid intravenous administration (RIA) of rifampicin in a dose of 10 mg/kg was studied on 173 healthy dogs. Immediately after the first RIA of rifampicin there were observed vomiting and ataxia of various levels in 5.2 per cent of the animals. After the drug administration their arterial pressure (AP) lowered to 50-60 mm Hg. By the 9th-11th minute it restored to the initial level. A collapse-like condition was recorded immediately after rifampicin RIA in 2.3 per cent of the dogs with marked decreasing of their AP up to 15-20 mm Hg. Its restoration to the initial level was slow and required 35-40 min. It was noted that after the third consecutive RIA of rifampicin the observed reaction disappeared. Probably this was due to adaptation of the host to rifampicin intravenous injections. Mezaton is an efficient agent rapidly arresting the reaction within 1-3 min.

Animals↗
PubMed1994

Intravenous administration among heroin users having treatment in Spain.

BACKGROUND: Of critical importance to AIDS control in Spain is the analysis of geographical variation and trend over time in the prevalence of intravenous administration in heroin users, as well as the factors associated with the use of this route. METHODS: We carried out a cross-sectional study of 27,655 people admitted to outpatient treatment for heroin dependence in 15 of the 17 Autonomous Communities of Spain during 1991, using data provided by the State Information System on Drug Abuse (SEIT). To assess the association of some factors with use of the intravenous route crude and logistic analysis was performed. RESULTS: The prevalence of intravenous administration in this population was 64.4% with regional differences ranging between 33% and 90%. Crude and logistic analysis demonstrated a strong association with two factors in addition to geography: the year of first use and the age at first use (the earlier the first use, the greater the strength of the association). CONCLUSIONS: These findings are of paramount importance for the control of the HIV epidemic in Spain and further study in this area could help to guide policy development.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Intraaortic balloon counterpulsation enhances coronary thrombolysis induced by intravenous administration of a thrombolytic agent.

OBJECTIVES: This study was designed to test the hypothesis that in the presence of moderate hypotension, intraaortic balloon counterpulsation would enhance coronary thrombolysis induced by intravenous administration of recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Although many studies have confirmed the efficacy of thrombolytic therapy in acute myocardial infarction, few have systematically investigated the effects of alterations in aortic pressure on coronary thrombolysis, and none have previously investigated the effects of intraaortic balloon counterpulsation on thrombolysis. METHODS: The effects of intraaortic balloon counterpulsation on aortic pressure, coronary blood flow and coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced in eight dogs by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, dogs underwent phlebotomy to decrease systolic aortic pressure to approximately 90 mm Hg. After phlebotomy, during a 15-min interval of intravenous administration of rt-PA, coronary thrombolysis and coronary flow were determined during and in the absence of counterpulsation. RESULTS: Intraaortic balloon counterpulsation significantly increased aortic diastolic pressure. Corresponding to the increase in pressure, intraaortic balloon counterpulsation significantly increased the rate of rt-PA-induced coronary thrombolysis. Although not statistically significant, peak diastolic coronary flow tended to increase with counterpulsation. CONCLUSIONS: These results indicate that in the presence of moderate systemic hypotension, intraaortic balloon counterpulsation enhances the rate of rt-PA-induced coronary thrombolysis.

Animals↗
PubMed2002

Widespread expression of an exogenous gene in the eye after intravenous administration.

PURPOSE: Gene-targeting technology and tissue-specific gene promoters were used to produce widespread expression of an exogenous gene throughout the eye, including the retinal pigmented epithelium, after noninvasive intravenous administration of a nonviral plasmid formulation. METHODS: An expression plasmid encoding bacterial beta-galactosidase, under the influence of either the simian virus (SV)40 promoter or the glial fibrillary acidic protein (GFAP) gene promoter, was packaged in the interior of 85-nm pegylated immunoliposomes (PIL) targeted to transferrin receptor (TfR)-rich structures with the rat 8D3 monoclonal antibody (mAb) to the mouse TfR. Plasmid DNA was packaged in the 8D3-PIL and injected intravenously into adult female BALB/c mice at a dose of 5 micro g DNA per mouse. The eyes were removed 48 hours later, and frozen sections were prepared for beta-galactosidase histochemistry and rhodopsin, TfR, or GFAP immunocytochemistry. RESULTS: There was diffuse expression of the SV40/beta-galactosidase gene in the retinal pigmented epithelium. The cellular specificity of gene expression was influenced by the promoter used in the gene construct, evidenced by the fact that gene expression in the inner retina was induced with the GFAP promoter. The beta-galactosidase gene was also widely expressed in the TfR-rich epithelial structures of the eye, including the ciliary body, the iris, the sebaceous glands of the tarsal plate, and the epithelium of the cornea. When the anti-TfR mAb on the PIL was replaced with the rat IgG isotype control, there was no gene expression in the eye. CONCLUSIONS: Widespread expression of an exogenous gene throughout the retina pigmented epithelium or other structures of the eye is possible with a noninvasive intravenous administration of a nonviral plasmid that is reformulated with gene-targeting technology. The cellular specificity of gene expression in the eye can be regulated with the use of cell-specific gene promoters.

Animals↗
PubMed1990

Quantitative determination of particulate contamination in intravenous administration sets.

Particle counts were performed on 1,000 intravenous administration sets from ten suppliers on the Swiss market using a HIAC/Royco electronic counter. The following main conclusions may be drawn from the results of this study: --the small particles were the most numerous, regardless of the type of set; --the differences in the counts obtained for the different suppliers' sets tended to level off for particles larger than 10 microns; --the drip chamber and latex connector may be two important sources of particles; --the particulate contamination from the sets is relatively low compared with the amount of particles contained in the parenteral solutions.

Drug Contamination↗
PubMed1990

[Sequential methotrexate.5FU chemotherapy for gastric cancer--comparison between intra-aortic infusion therapy and intravenous administration therapy].

Sequential low-dose Methotrexate.5FU therapy was conducted on a total 52 cases of advanced or recurrent gastric carcinoma. Intra-aortic infusion therapy was performed in 31 cases and intravenous administrative therapy was employed in the remaining 21 cases. The two groups were compared in terms of the response rate and side effects. Thirty mg/m2 of Methotrexate (MTX) was given by bolus injection into the aorta or venous route, followed by 500 mg or 750 mg of 5FU by bolus injection 3 hours later. Twenty four hours after the injection of MTX, 30 mg of Leucovorin was given intravenously or orally. The major lesion of intra-aortic infusion group was primary site (stomach) in 10 cases, peritoneum and digestive tract in 9 cases, Douglas' pouch in 5 cases, liver in 3 cases, abdominal wall in 2 cases and retro-peritoneal lymph nodes in 2 cases. On the other hand, the major lesion of the intravenous administrative group was the primary site (stomach) in 5 cases, peritoneum and digestive tract in 6 cases, Virchow's lymph-node in one, hepatic hilus in one and lung in one. Response could be evaluated in 31 patients with intra-aortic therapy. Partial response was found in 9 cases and NC in 16. PD was found in 5 and so the rate of response was 29.0% (9/31). The major lesion of 9 responders was inoperable Borrmann's Type 4 gastric cancer in 2 cases, peritoneal recurrence with an abdominal mass in 4, recurrence in the abdominal wall in one, Douglas' pouch in one, and intestinal stenosis in one.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Pharmacokinetics of morphine-6-glucuronide and its formation from morphine after intravenous administration.

BACKGROUND: Morphine-6-beta-glucuronide is a primary morphine metabolite with potent opioid action. However, its low and slow brain permeability eventually prevents its central opioid effects after short-term intravenous administration. Research is needed to establish whether morphine-6-beta-glucuronide qualifies as an analgesic; this study provides the pharmacokinetic bases for such studies. METHODS: Plasma concentration-time data of morphine-6-beta-glucuronide and morphine obtained from 20 healthy volunteers after short-term intravenous administration of either morphine-6-beta-glucuronide or morphine were described by a biexponential disposition curve. Disposition parameters of morphine-6-beta-glucuronide and morphine were estimated by nonlinear regression, and basic pharmacokinetic parameters (clearance, volume of distribution at steady state, and mean disposition residence time) were derived. A new model of metabolite kinetics was applied, and the disposition parameters of morphine and morphine-6-beta-glucuronide were then used to fit the plasma concentration-time profile of morphine-6-beta-glucuronide formed from morphine. Thereby the fraction of morphine metabolized to morphine-6-beta-glucuronide and the mean transit time of morphine across the site of metabolism were estimated. RESULTS: The extent and time course of morphine-6-beta-glucuronide formation from morphine could be well described by a parametric model, with a fraction of morphine metabolized to morphine-6-beta-glucuronide of 7.55% +/- 1.24% and a mean metabolic transit time for morphine to morphine-6-beta-glucuronide of 0.28 +/- 0.21 hour. The underlying disposition of morphine and morphine-6-beta-glucuronide was characterized by clearance (morphine clearance, 32.7 +/- 6 ml.min-1.kg-1, morphine-6-beta-glucuronide clearance, 2.2 +/- 0.4 ml.min-1.kg-1), volume of distribution at steady state (morphine, 1.8 +/- 0.3 L.hr-1; morphine-6-beta-glucuronide, 0.12 +/- 0.02 L.hr-1), and mean disposition residence time (morphine, 1.8 +/- 0.4 hours; morphine-6-beta-glucuronide, 1.7 +/- 0.4 hours). CONCLUSIONS: The time course of morphine-6-beta-glucuronide formation kinetics was analyzed with use of the information on the disposition kinetics of both morphine and preformed morphine-6-beta-glucuronide, which was obtained by separate data fits. The transformation of morphine to morphine-6-beta-glucuronide could be described by two parameters characterizing the extent and delay of metabolite formation. The results of this study will serve as pharmacokinetic bases of future investigations of morphine-6-beta-glucuronide in human beings.

Adult↗
PubMed2000

Pharmacokinetics of an everninomicin (SCH 27899) in mice, rats, rabbits, and cynomolgus monkeys following intravenous administration.

The pharmacokinetics of SCH 27899, a novel oligosaccharide compound of the everninomicin class with excellent activity against gram-positive strains, was studied with mice, rats, rabbits, and cynomolgus monkeys following intravenous administration as SCH 27899-N-methylglucamine-hydroxypropyl beta-cyclodextrin. Concentrations of SCH 27899 in mouse serum, rat plasma, and rabbit serum were determined by a high-pressure liquid chromatography method on a poly(styrene-divinyl benzene) column, and those in monkey plasma were determined by a paired-ion chromatographic method. Plasma and serum concentrations of SCH 27899 exhibited a biexponential decline in all species following intravenous administration. The half-lives at beta phase were 3.0 to 7.9 h in mice, rats, and rabbits and 24 h in cynomolgus monkeys. There was a linear relationship between the area under the curve extrapolated to infinity [AUC(I)] in mice and dose. Rabbits also exhibited dose proportionality in AUC(I). However, in rats, increasing the dose from 3 to 60 mg/kg of body weight resulted in a 49-fold increase in AUC(I). When the species was changed from mouse to rat, rabbit, or cynomolgus monkey, AUC(I) increased, whereas clearance (CL) decreased. It was concluded that the pharmacokinetics of SCH 27899 in animals varied with species; CL was the highest in mice and rats, followed by rabbits and cynomolgus monkeys.

Aminoglycosides↗