Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics, other analgesics and antipyretics, pyrazolones ATC code: N02BB02
Dipyrone is a pyrazolone derivative and it has analgesic, antipyretic and spasmolytic properties. The mechanism of action is not fully understood. Some research findings suggest that Dipyrone and the main metabolite (4-N methylamino-antipyrine) probably have both a central and a peripheral mechanism of action.

Pharmacokinetic Properties

5.2     Pharmacokinetic properties
Dipyrone is completely hydrolyzed to the pharmacologically effective 4-N methylamino-antipyrine (MAA) after oral application. The bioavailability of MAA is at approximately 90% and is slightly higher after oral administration than after parenteral administration. Simultaneous intake of meals does not have any relevant impact on the kinetics of Dipyrone.
The main metabolite of Dipyrone, MAA, is further metabolized in the liver by means of oxidation and hypomethylation, followed by acetylation.
The clinical efficacy is mainly based on MAA, to a certain extent also to the metabolite 4-amino- antipyrine (AA). The area-under the curve (AUC) values for AA represent approximately 25% of the AUC values for MAA.
The metabolites 4-N acetylamino-antipyrine (AAA) and 4-N formyl amino-antipyrine (FAA) are apparently pharmacologically inactive.
Please note that all metabolites have non-linear pharmacokinetics. A clinical significance of this phenomenon is not known. The accumulation of the metabolites is of low significance for short-term treatment.
Dipyrone passes the placenta. The metabolites of Dipyrone are excreted into breast milk.
The plasma protein binding is 58% for MAA, 48% for AA, 18% for FAA and 14% for AAA.
After administration of an oral single dose, 85% of the metabolites excreted in urine could be identified. Thereof, 3 ± 1 % were MAA, 6 ± 3 % AA, 26 ± 8 % AAA and 23 ± 4 % FAA. The renal clearance after an oral single dose of 1 g Dipyrone was 5 ± 2 for MAA, 38 ± 13 for AA, 61 ± 8 for AAA and 49 ± 5 ml/min for FAA. The corresponding-plasma half-lives were 2.7 ± 0.5 hours for MAA, 3.7 ± 1.3 hours for AA, 9.5 ± 1.5 hours for AAA and 11.2 ± 1.5 hours for FAA.
Elderly patients and patients with liver dysfunction
During treatment of elderly patients, the AUC value increased by a factor two to three. After a single oral dose, patients with liver cirrhosis experienced an approximately threefold increase in the half-life of MAA and FAA, whereas the half-lives of AA and AAA did not increase to the same extent. High doses should be avoided in these patients.
Children and adolescents
Children show a more rapid elimination of the metabolites than adults.
Renal dysfunctions
The available data from patients with impaired kidney function show reduced elimination velocity for some metabolites (AAA and FAA). Therefore, high doses should be avoided in these patients.