Gadobutrol

When ATH:
V08CA09

Pharmacological action.

The paramagnetic contrast agent for magnetic resonance imaging (MRT). Contrast enhancement is due to the active ingredient gadobutrol, which is a neutral complex paramagnetic gadolinium ion (III) a macrocyclic ligand - дигидрокси-гидроксиметилпропилтетраазациклододекан-триуксусной acid (butrolom). Induction of local oscillations of the magnetic field under the influence of strong magnetic moment gidoliniya at T2-weighted pulse sequence leads to a change in the signal from the tissue (contrasting effect).Gadobutrol even in low concentrations causes a significant shortening of the relaxation time. The ability to modify the relaxation times T1 and T2, determined from the effect on spin-lattice and spin-spin relaxation time of protons in plasma at pH 7 and 40 °C, It is quantitatively about 5,6 l / mmol s and • 6,5 l / mmol, respectively •. Ability to influence the relaxation times only to a small extent dependent on the strength of the magnetic field. Introduction gadobutrola provides a more accurate diagnostic information compared with the data, obtained in conventional MRI, in areas with high permeability of the BBB, or lack of it, lead to the violation of perfusion or an increase in the extracellular space, in such cases, the primary tumor, inflammatory and demyelinating zabolevaniy.Gadobutrol not activate the complement system, and so the likelihood of anaphylactoid reactions is very low. No inhibitory activity fermenty.Rezultaty clinical trials showed no negative effect on overall health gadobutrola, and liver function, kidney and cardiovascular system.

Pharmacokinetics

Similar to the pharmacokinetics of other biologically inert substances vysokogidrofilnyh, excreted by the kidneys (mannitol or inulin e.g.). Introduced in / gadobutrol is rapidly distributed in the extracellular space and in unchanged form excreted by the kidneys by glomerular filtration. It binds to plasma proteins krovi.Ekstrarenalnoe excretion of the drug is so small, that can not be ignored. Indicators proportional pharmacokinetics in humans administered dose gadobutrola. If the dose does not exceed gadobutrola 0,4 mmol / kg body weight, after the initial distribution phase and a phase of elimination of its level in the blood plasma decreases with a half-life 1,81 no (1,33-2.13), which corresponds to the rate of excretion by the kidneys. At a dose of gadobutrol 0,1 mmol / kg body weight via 2 min after its injection level in the blood plasma was 0,59 mmol / l, and through 60 min after injection - 0,3 mmol / l. During 2 h urine output more 50% of the administered dose, and for 12 h - more 90%. If the dose administered is gadobutrola 0,1 mmol / kg body weight, is 100 ± 2,6% of the dose is excreted from the body 72 no. Renal clearance of gadobutrol in healthy individuals is between 1,1 to 1,7 mL / min • kg; thus, it is comparable with inulin clearance, which indicates the preferential breeding gadobutrola by glomerular filtration. Less 0,1% administered substance excreted in the feces. Metabolites in the plasma and urine can not be detected. Half-life of gadobutrol in patients with impaired renal function increases in proportion to the degree of reduction of glomerular filtration. In patients with mild or moderate renal impairment gadobutrol completely excreted in the urine within 72 no. In patients with severely impaired renal function 80% of the administered dose is excreted in the urine within 120 no.

Testimony

Increasing contrast in MRI of the head and spine (cranial and spinal tomography).Introduction gadobutrola increases the possibility of obtaining diagnostic information in the fields, where the BBB is permeable or not, with altered perfusion or increased the size of the extracellular space, eg, in case of primary or secondary tumors, inflammatory and demyelinating diseases. For spinal MRI:- Differential diagnosis between intra- and extramedullary tumors; - Identification of the boundaries of solid tumors in the spinal canal and to determine the prevalence of intramedullary tumor. Gadobutrol has special advantages in the presence of the indications for the use of MRI contrast agents in high doses, in such cases,, when the identification or exclusion of additional lesions may affect the treatment, or medical tactics, as well as the detection of small lesions and for visualization of lesions, kontrastiruemyh difficult by conventional means. Gadobutrol shown for perfusion studies (in the diagnosis of stroke, recognition of focal cerebral ischemia and evaluation of tumor blood supply).

Dosage regimen

The desired dose is administered in / bolus. MRI with high contrast can be started shortly after injection (depending on the applied pulse sequence and study design). Optimal opacification is generally observed for about 15 minutes after administration of gadobutrol (this time depends on the characteristics and nature of tissue damage). Typically, high contrast persists until 45 minutes after administration of gadobutrol.

Using all the MRI contrast media can be observed side effects, nausea and vomiting. Therefore, to minimize the risk of vomiting and possible aspiration, the patient should refrain from eating for 2 h to issledovaniya.Pri / in a patient of a contrast agent (possibly) It must be in the supine position. After the introduction of gadobutrola patient should remain under medical supervision for at least 30 m, since, as the experience of the use of contrast agents, Most adverse events observed during this period. For studies with high contrast most suitable scanning T1-weighted pulse sequence. For perfusion studies of brain recommend the use of T2-weighted pulse sequences. Recruit gadobutrol in conventional syringe should only immediately prior to the study. Unused in a study of the drug must be destroyed. When selecting the dosing regimen for adults should be guided by the following rules. MRI of the head and spine (cranial and spinal tomography) usually, it is sufficient in / in a gadobutrola (1,0 mg / ml) dose 0,1 ml / kg body weight (equivalent 0,1 mmol / kg body weight).

If, despite the normal MRI with high contrast, remain suspicious of a disease, or if you need more accurate information on the number of, size and extent of lesions to develop tactics and medical treatment, diagnostic efficiency studies can be improved, Enter additional rr gadobutrola (1,0 mg / ml) at a dose of 0.1-0.2 ml 1 kg body weight for 30 minutes after the previous inektsii.Chtoby exclude metastases or tumor recurrence, introduced pp gadobutrola a dose 0,3 ml 1 kg body weight, which often contributes to the diagnostic efficacy studies. This applies to lesions with a weak network of blood vessels, Low extracellular space, or a combination of these factors, and the use of scanning relatively less intense T1-weighted pulse sequences. For perfusion studies of the brain is recommended T2- weighted pulse sequence in combination with MRI of the brain and spinal cord lesions to identify bulk or local ischemia in the absence of assumptions about the bulk lesions.

To carry out this study, it is recommended to use the injector; p-p hadobutrola (1,0 mg / ml) administered at a dose of 0,3 ml 1 kg body weight at a rate of 3-5 ml / sec.

If necessary, the dose can be increased to 0,5 ml / kg body weight.

In renal insufficiency, the dose of r-ra gadobutrola should be no higher 0,1 ml / kg body weight. Clinical experience with gadobutrol in patients younger than 18 years of absence.

Contraindications.

Hypersensitivity to gadobutrol.

Side effect.

From the body as a whole: bolus during or immediately after a transient sensation may occur unusual taste or smell; sometimes - nausea and vomiting; Cases of vasodilation and hypotension. It was also reported cases of transient headaches and dizziness. There have been reports of seizures, chills and fainting after the introduction of these drugs, however, a causal relationship with their introduction until proven. Allergic reactions: hypersensitivity reaction to the administration of gadobutrol more likely to develop in patients, allergy-prone. In rare cases anaphylactoid reactions accompanied by disturbances of breathing and other symptoms, a degree of anaphylactic shock. Sometimes, after the introduction of gadobutrola observed skin reactions (rash, hives). Local reactions: at the injection site due to venipuncture or injection of contrast agents may transient slight or moderate sensation of cold, heat or pain. Other: accidental introduction of gadobutrol in the perivascular tissue can cause pain lasting up to several minutes. Other tissue reactions were observed. Application gadobutrola in some cases may cause delayed (after a few hours or days) reaction.

Cautions

Be wary appoint gadobutrol in patients with severe renal impairment, because in this situation elimination of the contrast medium slowed. In severe cases, gadobutrol should be removed from the body by hemodialysis. After 3 courses of dialysis from the body is derived approximately 98% contrast agent. Hitherto renal dysfunction when administered drug were observed. Be wary appoint gadobutrol in patients with severe cardiovascular diseases, Although the relevant information is still limited. When using gadolinium magnetic resonance contrast agents reported occurrence in some cases, anaphylactoid reactions. Such reactions may also develop when using gadobutrola. The decision to use gadobutrola in patients with a predisposition to allergy should be carefully weighed, It is necessary to take into account the risk-benefit ratio. The study must have the tools and drugs for resuscitation. Gadobutrol, like other magnetic resonance contrast agents, containing gadolinium chelate, It requires special precautions when assigning patients with a low threshold for seizure activity. Pronounced state of excitation, anxiety and pain may increase the risk of adverse reactions or exacerbate adverse reactions, due to the introduction of a contrast agent.

Gadobutrol not recommended for use during pregnancy except in cases of emergency, since data on its application in this period no (Experimental studies have shown no embryotoxicity or teratogenic effect of the drug). In experimental studies found, that gadobutrol in minimal quantities (less 0,01% of the administered dose) It passes into breast milk. Therefore, after administration gadobutrola breastfeeding it is interrupted by at least 24 no.

Drug Interactions

The data is not provided.

Pezedozirovka

Until now, no marked. The risk of acute toxicity due to the use of gadobutrol maloveroyaten.V case of accidental overdose Gadobutrol may be removed from the body by extracorporeal dialysis.