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At least 433 records · Page 24Linked to original sources
PubMed1990

Clinical pharmacokinetics of intravenously injected tritiated vinzolidine.

Vinzolidine (VZL), a novel, semi-synthetic vinca alkaloid showing evidence of oncolytic activity in phase I/II clinical trials, was studied in six patients for its pharmacokinetic and metabolic behavior. Following i.v. administration of [3H]-VZL at doses of 5, 6.7, and 9 mg/m2, blood and urine samples were collected and analyzed by sample oxidation and HPLC. Following a single i.v. dose, decay of total tritium in plasma was tetraphasic, with a rapid initial t1/2 alpha of 0.044 +/- 0.013 h, followed by a t1/2 beta of 0.54 +/- 0.22 h and a t1/2 gamma of 9.48 +/- 4.89 h; the terminal t1/2 gamma was 219 +/- 57 h. The mean plasma clearance of total tritium was 0.054 +/- 0.044 l.kg/h, and the mean volume of distribution was 14.3 +/- 5.4 l/kg; mean urinary excretion was 13.6% +/- 4.3% of the delivered radioactivity. Qualitative analysis of plasma and urine revealed the predominance of unchanged VZL plus two unidentified metabolites with different elution times. In comparison with oral VZL, as previously reported, i.v. injected VZL showed comparable values with respect to the volume of the central compartment (VC), plasma clearance (Clp), and terminal t1/2 for total tritium. Qualitatively, the metabolites observed in plasma and urine were comparable in number and quantity with values obtained in analyses after oral administration.

Antineoplastic Agents, Phytogenic↗
PubMed1988

Serum vitamin D metabolites do not change in response to intravenous injection of thyrotropin releasing hormone (TRH) and growth hormone releasing factor (GHRF 1-44) in children.

Several reports claim that thyroid hormones and growth hormone participate in the regulation of vitamin D synthesis. We investigated whether there was a direct effect of their releasing hormones on vitamin D metabolism. TRH (7 micrograms/kg) was injected iv in 8 children with euthyroid diffuse goiter and GHRF (1 microgram/kg) in 10 short normal children. TRH injection induced significant TSH elevations but no changes in serum vitamin D metabolites, calcium and phosphorus. GHRF administration resulted in marked growth hormone elevations without alterations in the serum vitamin D metabolites, calcium and phosphorus. These results indicate no direct effect of TRH or GHRF itself on vitamin D metabolism, as well as a lack of very short term effect of growth hormone and TSH.

Calcifediol↗
PubMed2003

Fatal air embolism in an extremely low birth weight infant: can it be caused by intravenous injections during resuscitation?

OBJECTIVE: A preterm infant with a birth weight of 384 g who succumbed to vigorous resuscitation for sudden respiratory failure on the third day of life is presented. Postmortem examination revealed, apart from extensive pulmonary hemorrhage, a fatal amount of air mainly in the right ventricle. We believe that this air had been introduced via peripheral venous cannulas due to inadvertent and unavoidable air admixture to each injection volume administered with a syringe, and we develop an experimental model to confirm that fatal amounts of air can indeed accumulate with frequent change over of syringes within a short period of time. DESIGN: An empty 50-ml syringe was connected to a 15-cm-long connection line via a three-way tap. With a 1 ml syringe 100 doses of 0.5 ml aqua were injected into the connection line. The amount of air which had collected in the 50 ml syringe after the 100 injection cycles was measured. This process was repeated three times each by three of the authors and the average air volume introduced with 100 injections calculated for each investigator. RESULTS: The average amounts of air which had entered the closed system after 100 acts of syringe assembly and aqua administration were 1.84, 1.95, and 2.0 ml. This corresponds to an average volume of almost 0.02 ml per injection.

Embolism, Air↗
PubMed1999

Pharmacokinetics and biotransformations of oxaliplatin in comparison with ormaplatin following a single bolus intravenous injection in rats.

PURPOSE: Traditionally ultrafilterable Pt has been used to estimate the body exposure to platinum drugs. However, previous studies have shown that ultrafilterable Pt consists of both cytotoxic and inert biotransformation products of platinum drugs. Therefore, it has been proposed that pharmacokinetic parameters of the parent drug and its cytotoxic biotransformation products are more likely to be correlated with the drug toxicity and efficacy than those of ultrafilterable Pt. Oxaliplatin and ormaplatin are likely to form very similar biotransformation products in vivo based on previous studies. However, ormaplatin causes severe and irreversible neurotoxicity while oxaliplatin causes moderate and reversible neurotoxicity. To evaluate the hypothesis that the neurotoxicity is associated with the pharmacokinetics of active biotransformation products, we investigated the biotransformations and pharmacokinetics of oxaliplatin and ormaplatin in rats at equimolar doses. METHODS: 3H-oxaliplatin and 3H-ormaplatin were administered to Wistar male rats through single bolus i.v. injections (20 micromol/kg). Blood was sampled from 3.5 min to 360 min and centrifuged at 2000 g to separate the plasma from red blood cells (RBCs). The RBCs were sonicated and centrifuged at 13000 g to separate the cytosol from the membrane fraction. Both plasma and RBC cytosol were filtered through YMT30 membranes (Mr = 30000 kDa), and the ultrafiltrates were analyzed using a single column HPLC technique to identify and quantitate the biotransformation products. The pharmacokinetics of oxaliplatin, ormaplatin, and their biotransformation products were characterized utilizing the curve stripping and nonlinear least-squares fitting program RSTRIP. RESULTS: The decays of total, plasma, plasma ultrafilterable (PUF), RBC-bound, and plasma protein-bound Pt-dach (only Pt species with an intact dach carrier ligand were quantitated in this study) were described by biphasic curves. No significant kinetic differences between oxaliplatin and ormaplatin were observed for total, plasma, and PUF Pt-dach in the initial alpha decay phase. However, Pt-dach bound to plasma proteins fourfold more quickly for ormaplatin than for oxaliplatin, and the AUC for Pt-dach bound to plasma proteins was twofold higher for ormaplatin than for oxaliplatin. The concentration of RBC-bound Pt-dach was highest at the initial time-point of 3.5 min for both drugs, which suggested a very rapid RBC uptake. The binding of Pt-dach to RBCs was slightly greater initially for ormaplatin than for oxaliplatin. However, the RBC-bound Pt-dach decayed more rapidly for ormaplatin (t(1/2alphaRBC) = 5.1 min) than for oxaliplatin (t(1,2alphaRBC) = 15.3 min). Thus the AUC(RBC) was slightly greater for oxaliplatin than for ormaplatin. The AUC was also slightly greater for oxaliplatin than for ormaplatin for the Pt-dach associated with the RBC membrane and RBC cytosolic proteins. However, there was no significant difference between oxaliplatin and ormaplatin for Pt-dach in the RBC cytosolic ultrafiltrate. There was also no significant difference in the AUCpuf between oxaliplatin and ormaplatin. Both oxaliplatin and ormaplatin produced the same types of major plasma biotransformation products including Pt(dach)Cl2, Pt(dach)(Cys)2, Pt(dach)(GSH)2, Pt(dach)(GSH), Pt(dach)(Met), and free dach. The decays of oxaliplatin, ormaplatin, and their biotransformation products were described by biphasic curves. (ABSTRACT TRUNCATED)

Animals↗
PubMed1997

[Signal improvement of pulmonary venous Doppler flow prifile after intravenous injection of levovist].

The analysis of the pulmonary venous flow Doppler pattern can assist in the determination of the severity of mitral regurgitation and, in conjunction with transmitral flow pattern, the assessment of left ventricular diastolic dysfunction. In about one third of the cases, however, transthoracic ultrasonography is not able to record an adequately analyzable pulmonary venous flow pattern. The aim of the study was to examine and compare the effect of the echo-enhancing agent Levovist on the pulsed-wave Doppler flow quality of the transthoracically (TTE) and transesophageally (TEE) recorded pulmonary venous flow. In 26 consecutive patients, a qualitative (score system) and quantitative analysis of the pulmonary venous flow pattern was obtained before and after peripheral venous injection of Levovist at concentrations of 200 mg/ml (low dose) and 400 mg/ml (high dose). The number of measurable studies for the antegrade pulmonary venous flow increased after Levovist from 85% to 96% for TTE and from 96% to 100% for TEE. The retrograde flow as seen by TTE was adequately analyzable in only 45% before and in 73% after injection of Levovist (p < 0.02). Before any contrast enhancement, the retrograde pulmonary venous flow recorded by TEE could be analyzed in 77% of the patients with the percentage increasing to 88% and 92% after administration of a low and high dose of Levovist, respectively (p < 0.05). In particular, the quality score of the retrograde flow was significantly altered by the administration of Levovist (increase from 1.8 +/- 1.0 to 2.6 +/- 1.1 (low dose Levovist), p < 0.05 and to 2.7 +/- 1.3 (high dose Levovist). p < 0.05). The pulsed-wave Doppler evaluation by TTE without Levovist underestimated the velocities of the antegrade and retrograde pulmonary venous flow After administration of Levovist, the recorded values are comparable to those obtained by TEE. An analogous pattern is encountered when quantifying the duration of the retrograde flow component. Thus, the peripheral venous injection of Levovist leads to an improved quality of the pulmonary venous flow Doppler signal recorded by TTE. Qualitatively and quantitatively the values recorded by TTE after administration of Levovist are comparable to those of the TEE technique without an echo-enhancing agent.

Adult↗