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Results for “Administration, Intravenous”

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PubMed2001

Neuroprotection in transient focal brain ischemia after delayed intravenous administration of brain-derived neurotrophic factor conjugated to a blood-brain barrier drug targeting system.

BACKGROUND AND PURPOSE: Neuroprotection with brain-derived neurotrophic factor (BDNF) requires direct injection into the brain owing to poor transport of the neurotrophin through the blood-brain barrier (BBB) in vivo. The present studies investigate whether BDNF alone or conjugated to a BBB drug targeting system is neuroprotective in focal, reversible brain ischemia after delayed intravenous administration at 60 or 120 minutes after middle cerebral arterial occlusion. METHODS: BDNF was conjugated to the OX26 murine monoclonal antibody to the rat transferrin receptor, which undergoes transport into brain from blood via the BBB transferrin receptor transcytosis system. After a 1-hour occlusion of the middle cerebral artery in nitrous oxide- ventilated animals with normal blood sugar, the brain was reperfused, and either BDNF or the BDNF/OX26 conjugate was administered as a single intravenous injection at a dose of 50 microg per rat. RESULTS: After the intravenous administration of unconjugated BDNF, there was no neuroprotection on the basis of analysis of brain at either 24 hours or 7 days after a 1-hour middle cerebral arterial occlusion. In contrast, there was a 68% and 70% reduction in cortical stroke volume at 24 hours and 7 days, respectively, after intravenous administration of 50 microg per rat of the BDNF conjugate (P<0.01). No effects on subcortical stroke volume were observed. CONCLUSIONS: These studies demonstrate marked neuroprotection in focal, transient brain ischemia with a single, delayed intravenous injection of BDNF if the neurotrophin is conjugated to a BBB drug targeting system. The neuroprotection is long lasting and persists for at least 7 days after a 1-hour middle cerebral artery occlusion.

Animals↗

PubMed1996

Effect of intravenous administration of fluids on packed cell volume, blood pressure, and total protein and blood glucose concentrations in healthy halothane-anesthetized dogs.

OBJECTIVE: To determine the effects of IV administration of fluids on PCV, serum total protein and blood glucose concentrations, and systolic arterial pressure in healthy anesthetized dogs undergoing elective surgical procedures. DESIGN: Prospective, randomized controlled trial. ANIMALS: 70 clinically normal dogs. PROCEDURE: Dogs received i.v. administration of 0, 5, 10, or 15 mL/kg of body weight/h of a polyionic crystalloid solution or 5% dextrose in water. Blood samples were collected before and after administration of medication, prior to anesthetic induction, after anesthetic induction, at the end of the surgical procedure, and 2 hours after surgery to determine PCV and serum total protein and blood glucose concentrations. Blood pressure was measured before and after anesthetic induction and at the end of the surgery. RESULTS: There were not any significant differences in PCV, total protein concentration, or systolic arterial pressure among treatment groups. Hyperglycemia developed in dogs receiving 5% dextrose in water, but resolved 2 hours after discontinuing administration of fluids. CLINICAL IMPLICATIONS: Intravenous administration of fluids may not be necessary to maintain normal blood pressure in young, healthy dogs undergoing elective surgery.

Anesthesia, Inhalation↗

PubMed2000

Development and validation of a recirculatory physiological model of the myocardial concentrations of lignocaine after intravenous administration in sheep.

A recirculatory physiological model of the determinants of the myocardial concentrations of lignocaine after intravenous administration was developed in sheep and validated with the intention of analysing and predicting the outcome of altered dose regimens and various pathophysiological states on the initial myocardial concentrations of lignocaine. The structure and parameters of the model were determined by hybrid modelling of the time-courses of the pulmonary artery, arterial and coronary sinus concentrations of lignocaine after the intravenous administration of 100 mg of lignocaine over 5 min to 5 chronically instrumented sheep. The model accounted for the determinants of the myocardial concentrations via compartments for venous mixing, the lung (a single-compartment model with a first-order loss) and the heart (a single flow-limited compartment). Recirculation and the remainder of the body were represented as a single tissue pool with a clearance term. The distribution volume of the heart was 0.42+/-0.009 L, which gave a half-time of myocardium:blood equilibration of 2.37 min. The distribution volume of the lungs was 5.40+/-0.23 L, with an apparent first-order loss of 1.02 L min(-1) representing deep distribution or metabolism. The validity of the model was tested by comparing the predictions of the model with the equivalent data collected in 6 sheep when lignocaine (89 mg) was administered via a complex dose regimen with a faster initial rate of infusion (39.1 mg min(-1)), declining exponentially to basal infusion rate (7.02 mg min(-1)) over 8 min. The predictions of the model were in general agreement with these data. It is concluded that the model was sufficient to account for the effect of altered dose regimens of lignocaine on the time-course of its myocardial concentrations.

Anesthetics, Local↗

PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 10). Testicular toxicity of adriamycin observed 2 and 4 weeks after a single intravenous administration.

The present study was performed to clarify whether toxic effects of the antitumor drug, adriamycin (ADR) on the male genital organ can be adequately detected 2 and 4 weeks after a single intravenous administration in the rat. ADR was intravenously administered once to 10 Crj:CD (SD) male rats/group aged 6 weeks (4-week group) and 8 weeks (2-week group) at doses of 0, 2 and 6 mg/kg. The rats were sacrificed at the age of 10 weeks. For comparison 10 rats/group were killed 2 weeks after a single intravenous administration at the age of 4 weeks (immature group). Saline was administered to control rats. Histopathological examination and a quantitative morphometry were carried out after measurement of testes weights at necropsy. In rats of the 4-week and 2-week groups, mean absolute testicular weight in all groups was significantly decreased. However, changes in mean relative weight were not evident in the 2-week group. Disappearance of seminiferous epithelial cells was observed histopathologically in rats dosed with 2 and 6 mg/kg in the 2-week group. The change was more severe in the 4-week group, when reduction of spermatogenesis and giant cells were also observed at 6 mg/kg. The quantitative morphometry in the 2-week group showed decreases in the numbers of spermatogonia and spermatocytes in stages X and XII at 2 mg/kg, and in the numbers of spermatogonia in all stages and spermatocytes in all stages except stage V at 6 mg/kg. Moreover, the numbers of spermatogonia and spermatocytes in all stages and spermatids in stages II-III and V were decreased with dose related manner in the 4-week group. In contrast, no obvious change in testes weights was apparent in the immature group. However, the numbers of spermatogonia and spermatocytes in all stages were decreased at 6 mg/kg. In conclusion, testicular toxicity of ADR could be detected 2 weeks after a single administration. Susceptibility of the testes of immature rats to ADR might be less than that of older animals.

Animals↗

PubMed1997

The pharmacokinetics of topotecan and its carboxylate form following separate intravenous administration to the dog.

PURPOSE: To determine the relationship between topotecan and its ring opened hydrolysis product (SK&F 105,992) following intravenous administration of the two agents separately, and to determine the bio-availability of topotecan in female beagle dogs. METHODS: The pharmacokinetics of topotecan and SK&F 105,992 were determined following separate administration as 30 minute intravenous infusions in a cross-over design. Topotecan was also administered orally to the same dogs. RESULTS: When administered intravenously to dogs, SK&F 105,992 underwent interconversion to topotecan. Plasma concentrations of both topotecan and SK&F 105,992 appeared to decline multi-exponentially following i.v. infusion of either compound. A 2-compartment model was found to adequately characterize the data. CONCLUSIONS: The clearance of topotecan by other routes proceeded at a faster rate than its interconversion to SK&F 105,992, whereas the clearance of SK&F 105,992 by other routes was slower than the rate of its interconversion to topotecan. Any SK&F 105,992 formed in the GI tract did not appear to be well absorbed following oral administration of topotecan to dogs. The steady-state volume of distribution for topotecan was approximately 8- to 9-fold greater than that for SK&F 105,992 in the dog. After intravenous administration of topotecan, the amount of topotecan in the dog was much greater than that of the carboxylate, even though their respective plasma concentrations were similar. The bioavailability of topotecan, calculated from oral topotecan data or from SK&F 105,992 data, was approximately 50%.

Administration, Oral↗

PubMed1983

[Effect of intravenous administration of micronomicin on the inner ear of guinea pigs].

The present experiment was made to clarify the effect of intravenous administration of micronomicin (sagamicin, MCR) on the inner ear of guinea pigs (300--350 g). MCR was given to the animals intravenously at dose of 25, 50 mg/kg and 100 mg/kg, respectively for 28 days. Pinna reflex test in frequency range from 20 kHz to 0.5 kHz was performed before, during and after the administration. The temporal bones were removed after intravital perfusion of the inner ears with neutral formation after the end of the administration. Histopathological examination was performed on the serial celloidin sections of the inner ears which had been stained with hematoxylin eosin. The following results were obtained. 1. MCR had a mild corti toxicity, which did not show remarkable dose dependent increase. 2. MCR had more affinity for the vestibular organs than for the organ of corti. The affinity for the vestibular organ increased with increase in dose. 3. MCR showed less increase in corti toxicity in intravenous administration than in intramuscular injection. However, the affinity of MCR for the vestibular organ showed little more increase in the intravenous administration than in the intramuscular injection.

Aminoglycosides↗

PubMed1993

Effect of oral activated charcoal on propranolol pharmacokinetics following intravenous administration to rabbits.

The pharmacokinetics of propranolol following intravenous administration (1 mg/kg), with and without treatment with oral activated charcoal, was investigated in rabbits. In charcoal-treated rabbits a significant reduction in propranolol serum concentrations was observed compared to control animals. Charcoal treatment significantly reduced the half-life of elimination (16.6%) and the mean residence time (19%) of propranolol. A 17% increase in the systemic clearance and a 14% decrease in AUC were also noted. Charcoal administration did not significantly alter the volume of distribution (Vc' V(area) and Vss) or the apparent distribution half-life. A two-compartment model adequately described propranolol in control and treated rabbits. The results indicate that administration of oral activated charcoal enhances the systemic elimination of propranolol. This is presumably mediated by interruption of the enterohepatic circulation of propranolol by activated charcoal.

Administration, Oral↗

PubMed1976

Relationships between the concentrations of doxycycline in serum and in thoracic duct lymph after oral and intravenous administration in man.

The concentrations of doxycycline in serum and in thoracic duct lymph at various times after oral and intravenous administration of 200 mg of the drug were determined in 10 patients subjected to thoracic duct cannulation for diagnostic purposes. After oral administration, a mean peak serum concentration of 2.4 mug/ml (n=7) was obtained within 3 h; then the levels successively declined. The concentrations in thoracic lymph were lower, a mean peak concentration of 1.6 mug/ml being found 3 and 6 h after the intake. After intravenous administration (n=3), the concentrations of doxycycline in thoracic duct lymph were lower than but closely followed those in serum. The difference in concentrations between serum and lymph 1-6 h after the start of the infusion never exceeded 30%. The results suggest that doxycycline is rapidly distributed to the extracellular tissue fluids.

Administration, Oral↗

PubMed2003

Effect of indinavir on the intestinal exsorption of amprenavir, saquinavir and nelfinavir after intravenous administration in rats.

To elucidate drug interaction between human immunodeficiency virus (HIV) protease inhibitors (PIs), the effect of indinavir (IDV) on the intestinal exsorption of other HIV PIs, amprenavir (APV), saquinavir (SQV) and nelfinavir (NFV) was investigated in rats using an in situ single perfusion method. IDV in the intestinal perfusate inhibited the exsorption of rhodamine 123 (Rho123), a known P-glycoprotein (P-gp) substrate, from blood into intestinal lumen in a concentration-dependent manner, and the inhibitory potency of 10 micro M IDV in the perfusate was close to that of 10 micro M cyclosporin A (CsA) in the perfusate. Ten micro M of IDV in the intestinal perfusate also decreased significantly the exsorption clearance of Rho123 after intravenous administration. The IDV concentration in this system was not likely to cause hepatic interaction between HIV PIs, because the plasma IDV concentration was far below its inhibition constants for other HIV PIs in the liver microsomes. Thus, 10 micro M of IDV was chosen to investigate the effect of this inhibition on the exsorption of APV, SQV and NFV. IDV in the intestinal perfusate markedly increased the exsorbed amounts of SQV and NFV but not APV after intravenous administrations. Their exsorption clearances, however, showed only a slight increasing tendency or remained unchanged. These findings suggest that in addition to P-gp inhibition, other factors such as CYP3A inhibition might be important in the drug interaction of IDV with APV, SQV and NFV after intravenous administration in rat small intestine. The results obtained in this study will provide useful information to discuss the interactions among PIs when a double protease therapy is used for in HIV-infected patients.

Animals↗

PubMed2000

Effects of anesthesia, surgery, and intravenous administration of fluids on plasma antidiuretic hormone concentrations in healthy dogs.

OBJECTIVE: To evaluate effects of anesthesia, surgery, and intravenous administration of fluids on plasma concentrations of antidiuretic hormone (ADH), concentration of total solids (TS), PCV, arterial blood pressure (BP), plasma osmolality, and urine output in healthy dogs. ANIMALS: 22 healthy Beagles. PROCEDURE: 11 dogs did not receive fluids, and 11 received 20 ml of lactated Ringer's solution/kg of body weight/h. Plasma ADH adn TS concentrations, PCV, osmolality, and arterial BP were measured before anesthesia (T0) and after administration of preanesthetic agents (T1), induction of anesthesia (T2), and 1 and 2 hours of surgery (T3 and T4, respectively). Urine output was measured at T3 and T4. RESULTS: ADH concentrations increased at T1, T3, and T4, compared with concentrations at T0. Concentration of TS and PCV decreased at all times after administration of preanesthetic drugs. Plasma ADH concentration was less at T3 in dogs that received fluids, compared with those that did not. Blood pressure did not differ between groups, and osmolality did not increase > 1% from To value at any time. At T4, rate of urine production was less in dogs that did not receive fluids, compared with those that did. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentration increased and PCV and TS concentration decreased in response to anesthesia and surgery. Intravenous administration of fluids resulted in increased urine output but had no effect on ADH concentration or arterial BP. The causes and effects of increased plasma ADH concentrations may affect efficacious administration of fluids during the perioperative period in dogs.

Anesthesia↗

PubMed1986

Study of the tolerance and diuretic properties of torasemide following oral or intravenous administration to healthy volunteers.

The tolerance and diuretic properties of torasemide after oral or intravenous administration to healthy volunteers were studied. Six groups, each of 6 subjects, were given single rising oral doses ranging from 10 to 100 mg; 8 subjects received ascending i.v. doses on alternate days, ranging from 2.5 to 80 mg. At the highest oral doses investigated (80 mg and 100 mg) a number of volunteers complained of cramps in the knees, calves and feet. These symptoms were generally of short duration. Similar effects were not encountered during the intravenous study. There were no significant changes in ECG. Some significant drug-related changes were encountered in the within-study biochemistry and haematology assessments. Torasemide proved to be a potent diuretic following oral administration at all the doses investigated and following intravenous administration at all doses except 2.5 mg. A linear relationship existed between the urine output and the logarithm of the dose, and both sodium and chloride excretion were linearly correlated with urine volume. The rate of potassium excretion was markedly lower than that of sodium and chloride and was linearly correlated with the logarithm of the urine volume. Torasemide was well tolerated from all perspectives studied. It showed a potent diuretic property, and was equally effective by the oral and intravenous routes.

Administration, Oral↗

PubMed1983

Pharmacokinetics and protein binding of prednisolone after oral and intravenous administration.

The pharmacokinetics of prednisolone after oral and intravenous administration of 10 and 20 mg have been studied. Serum protein binding of prednisolone was also measured after the i.v. injections. The bioavailability after oral administration was 84.5% after 10 mg and 77.6% after 20 mg (p greater than 0.05). Dose dependent pharmacokinetics were found, the VDss and Clt being significantly larger (p less than 0.01) after 20 mg i.v. than after 10 mg i.v. The protein binding of prednisolone in all subjects was non-linear, and is the most likely cause of the dose dependent pharmacokinetics, as there was no dose dependent variation in elimination half-time.

Administration, Oral↗

PubMed1979

The hypotensive response to rapid intravenous administration of hypertonic solutions in man and in the rabbit.

Transient hypotension has been observed in patients after rapid intravenous administration of mannitol, 25 per cent, in clinical doses. These studies were conducted to determine the mechanism for the hypotension, to determine dose and rate of injection response curves in rabbits, and to determine which vascular beds were most reactive. Studies in six patients showed mean decreases in blood pressure of 23 +/- 6.0 per cent (+/-SE) and in total peripheral resistance of 38 +/- 7 per cent after infusion of mannitol. Studies in 18 patients during cardiopulmonary bypass with mechanically fixed cardiac output demonstrated decreases in mean blood pressure of 30 +/- 5 to 40 +/- 3 per cent, depending on dose and rate of administration of mannitol. Patients not on bypass compensated for large decreases in total peripheral resistance by increases in cardiac output (3.6 +/- .4 at baseline to 4.4 +/- .4 l/min) during mannitol-induced hypotension with no change in heart rate. Serum osmolality increased as blood pressure decreased. Significant but clinically unimportant decreases in sodium and potassium ions, hemoglobin, pH, and base excess values were observed. Studies in 18 rabbits showed that the greater the dose or rate of injection of mannitol the greater the decrease in blood pressure. Injection of radiolabeled microspheres in rabbits demonstrated a near doubling of blood flow to skeletal muscle tissue during the hypotension. This occurred with both equiosmotic hypertonic glucose (17 +/- 3 to 32 +/- 7 per cent) and mannitol (17 +/- 1 to 31 +/- 5 per cent), but not after isotonic saline solution. Changes in blood flow to other organ beds were variable and unimportant. The results suggest that hypotension following the intravenous administration of hyperosmotic solutions is due primarily to vasodilation in skeletal muscle.

Acid-Base Equilibrium↗

PubMed1984

Serum and myocardial kinetics of amiodarone and its deethyl metabolite after intravenous administration in rabbits.

The serum kinetics of amiodarone and its major metabolite the deethyl analogue were studied in rabbits after intravenous administration. The elimination of the drug and the metabolite from serum occurred as a biexponential function. Both compounds exhibited a rapid distribution phase (6.5 and 4.4 min, respectively) and had elimination half-lives of 136 and 235 min, respectively. There was a rapid uptake of both drugs by the myocardium, with maximal concentrations at 5 and 15 min. The myocardial concentrations were higher than the respective serum concentrations and declined with time. There was a wide scatter in myocardium-serum ratios, which ranged from 1 to 11 for amiodarone and 12 to 29 for the metabolite. Neither the drug nor the metabolite produced significant changes in the surface electrocardiogram after intravenous administration. These data suggest that accumulation of the metabolite does not account for the slow onset of action of amiodarone.

Amiodarone↗

PubMed1995

In vivo production of various cytokines in splenocytes of sheep erythrocyte-immunized mice after intravenous administration of bacterial lipid A.

The effects of an intravenous administration of lipid A from Salmonella minnesota R595 lipopolysaccharide on the in vivo production of interleukin-2 (IL-2), IL-4, IL-5 and IL-6 in the spleens of mice intravenously immunized with sheep red blood cell (SRBC) antigen were investigated. The increased number of antigen-specific IgM antibody-producing cells and the titer of the IgM serum antibody were measured using the plaque-forming cell (PFC) assay and an enzyme-linked immunosorbent assay (ELISA). Simultaneous injections of SRBC antigen and lipid A adjuvant enhanced IgM-PFC number on days 3 and 4 and the serum IgM titer on days 4 and 5 after the immunization. We found that the enhanced IL-4 and IL-5 levels correlated with the PFC number and IgM titer. When lipid A was injected intravenously 2 days after immunization with SRBC, the PFC number in lipid A-treated groups were similar to those in controls 3 and 4 days after the immunization. However, it was found that a twofold increase in the IgM titer in serum was induced by lipid A 5 days after immunization. In relation to this increase, lipid A stimulated the production of only IL-5 among the cytokines tested.

Animals↗

PubMed2003

Evidence for the involvement of a pulmonary first-pass effect via carboxylesterase in the disposition of a propranolol ester derivative after intravenous administration.

The disposition kinetics of O-butyryl propranolol (butyryl-PL), a model compound containing an ester moiety, after intravenous administration was compared with that of PL in rats and beagle dogs. Rats showed only 30% conversion of butyryl-PL to PL up to 2 h after dosing, whereas dogs showed nearly complete conversion within 10 min after administration. The CL(total) of butyryl-PL in rats was 5.8 l/h/kg and that in dogs was 65.6 +/- 18.6 l/h/kg, both of which were greater than hepatic blood flow. The in vivo conversion from butyryl-PL to PL in the rat could be explained on the basis of the hydrolysis characteristics in the liver and blood. The in vitro hydrolysis data and the in vivo data after intra-arterial administration clearly demonstrated that the extremely high CL(total) of butyryl-PL in dogs was dependent on first-pass hydrolysis in the lung in addition to hydrolysis at a blood flow-limited rate in the liver and kidney. The availability of butyryl-PL after passage through the lung was 50%. Furthermore, the isoform of carboxylesterase involved in the pulmonary hydrolysis of butyryl-PL in the dog was identified as D1, a CES-1 group enzyme. However, butyryl-PL was not recognized as a substrate by CES-1 family carboxylesterases, which are present at high levels in the rat lung (RH-1) and kidney (RL-1). These findings indicate that extrahepatic metabolism, especially in the lung, is important in the disposition of drugs containing an ester moiety after intravenous administration and that the substrate specificity of carboxylesterase isozyme distinguishes from others.

Adrenergic beta-Antagonists↗

PubMed1989

[The anti-arrhythmia effect and hemodynamic effects of Bonnecor in intravenous administration].

For testing the efficiency of Bonnecor in intravenous administration (0.3 mg/kg) 36 patients were examined electrophysiologically (31 with paroxysmal supraventricular tachycardias, 5 with ventricular tachycardias). In other 6 patients haemodynamic investigations were performed by means of right-heart catheterization and thermodilution. The supraventricular tachycardias induced by programmed electrostimulation could be interrupted by administration of Bonnecor in 45% of the cases. After the administration of Bonnecor the inducibility of supraventricular tachycardias was suppressed in 11 of the 31 patients. In 2 of the 5 patients with ventricular tachycardia an evocation of ventricular tachycardias was no more possible after an intravenous application of Bonnecor; a medicamentous termination of the ventricular tachycardias had been tried only in one case. Clinically relevant negatively inotropic effects could not be proved. Apart from insignificant malaises in few cases, no side-effects occurred.

Adult↗

PubMed1993

Intravitreal ganciclovir concentration after intravenous administration in AIDS patients with cytomegalovirus retinitis: implications for therapy.

To determine whether therapeutic intravitreal concentrations of ganciclovir are achieved after intravenous administration, vitreous samples were obtained intraoperatively from 23 eyes of 22 AIDS patients with retinal detachments associated with cytomegalovirus (CMV) retinitis. The mean intravitreal ganciclovir concentration of all samples was 0.93 +/- 0.39 microgram/mL (3.6 +/- 1.5 microM). This level is near the published trough serum concentrations obtained with every-12-h intravenous dosing and well below the peak. It is significantly below the concentration of ganciclovir required to achieve 50% of viral plaque formation for many human CMV strains. Only a small decrease in vitreous drug levels was observed as a function of time after last dose. Intravenous administration of ganciclovir results in near-steady-state subtherapeutic intravitreal ganciclovir concentrations for many CMV isolates. This may explain the difficulty of long-term complete suppression of CMV retinitis.

AIDS-Related Opportunistic Infections↗