Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antispasmodic urological including drug
ATC code: G04B D09
Trospium chloride, a quaternary ammonium derivative of nortropanol belongs to the group of parasympatholytic or anticholinergic compounds. Depending on the concentration, the drug competes with the endogenous transmitter acetylcholine for postsynaptic binding sites. The drug has a high affinity for the M1 - and M3-receptors and in comparison a lower affinity for the M2-receptor and binds to nicotinic receptors at a negligibly low rate.
Trospium chloride has a considerable relaxing effect on smooth muscles and organs due to its antimuscarinic properties which are transmitted through the muscarine receptors.
Trospium chloride reduces the tension of the smooth muscles in the gastrointestinal and urogenital tract. It inhibits the bronchial, salivary and sweat secretion and paralyses accommodation. Central effects have not been observed up till now.
In two specific safety studies in healthy volunteers trospium chloride has been proven not to affect cardiac repolarisation, but has been shown to have a consistent and dose dependent heart rate accelerating effect.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Maximal blood levels of trospium chloride are reached four to six hours following oral administration. The elimination half-life is very variable and ranges between 5 and 18 hours after oral application. There is no accumulation. The plasma protein binding rate is 50-80%.In the dose range of 20 to 60 mg as single dose the plasma levels are linear to the applied dose. The predominant portion of systemically available trospium chloride is excreted largely unchanged via the renal system. A small portion is excreted as spiro-alcohol (ca. 10%), a metabolite formed by hydrolysis of the ester.
Special patient groups
Pharmacokinetic data did not reveal any major differences in elderly patients or between genders.
Simultaneous food intake results in reduced bioavailability but more homogenous plasma levels.
With the knowledge that equivalence of efficacy of trospium chloride immediate release formulations has been proven compared to oxybutynin, without prescribing ingestion under fasting conditions, there is no need to take Spasmex film-coated tablets under fasting conditions.
Trospium chloride exhibits diurnal variability in exposure with decrease in both Cmax and AUC for lunchtime and evening in relation to morning doses.
In a study involving patients suffering from moderate to severe renal impairment (Cockcroft-Gault formula estimated creatinine clearance < 50 mL/ min) the mean AUC was found to be 5-fold and the Cmax to be 4.5-fold increased. The half-life was prolonged (1.7-fold) in comparison to healthy persons. No marked differences with regard to AUC and Cmax were found between healthy subjects and patients with mild renal impairment (creatinine clearance 50-80 mL / min).
Results from a pharmacokinetic study on patients with mild to moderate impairment in live function did not reveal the necessity of dose adjustment in this group of patients.