Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Contact Laxatives
ATC code: A06A B58

The active components of PICO-SALAX are sodium picosulfate and magnesium citrate. S odium picosulfate is a locally acting stimulant cathartic, which after bacterial cleavage in the colon forms the active laxative compound, bis-(p- hydroxyphenyl)-pyridyl-2-methane (BHPM), which has a dual-action with stimulation of the mucosa of both the large intestine and of the rectum. Magnesium citrate acts as an osmotic laxative by retaining moisture in the colon. The combined action of the two substances is of a 'washing out' effect combined with peristaltic stimulation to clear the bowel.
The product is not intended for use as a routine laxative.

Clinical efficacy and safety
The dosing regimen as described in section 4.2 Posology, and herein further referred to as the tailored dosing regimen, was investigated and evaluated in trial 000121 (OPTIMA) The efficacy, safety and tolerability of PICO-SALAX administered according to the tailored dosing regimen was compared with the fixed schedule of dosing (i.e. first dose is taken before 8am and second dose is taken 6-8 hours later on the day before procedure), called Day- before dosing regimen (204 patients were randomized, 131 received tailored dosing, 73 received day before dosing).


Superiority of the tailored dosing regimen was demonstrated compared to the day before dosing regimen in overall colon cleansing and responder status for ascending colon cleansing. For overall colon cleansing (primary endpoint), the tailored dosing regimen was compared to the Day -before dosing regimen, based on the treatment difference in mean total Ottawa Scale score (4.26 versus 8.19 in mean total Ottawa scale score for tailored dosing regimen and Day- before dosing regimen respectively, with a corresponding p-value <0.0001, for the Intend to Treat (ITT) analysis set). For the responder status of the ascending colon (key secondary endpoint), the proportion of patients with an Ottawa Scale score of either 0 (excellent) or 1 (good), was compared between the tailored dosing regimen and the Day- before dosing regimen.
Patients randomized to the tailored dosing regimen were observed to have a 4.05 times greater chance of being a responder with respect to ascending colon cleansing compared to patients randomized to the Day -before dosing regimen.
Endpoint                             Study        PICO-SALAX day         PICO-SALAX tailored Population   before dosing          dosing regimen
(n=204)      regimen                Estimate (95%CI)
Estimate               (n=131)
(n=73)
Mean Total Ottawa Scale              ITT          8.19                   4.26 Score                                                                    -3.93(-4.99,-2.87) (Adjusted estimate)                                                      p-value < 0.0001 Proportion of patients with          ITT          15.1%                  61.1% an Ottawa Scale score of                                                 RD* 0.46 (0.34; 0.58) either 0(excellent) or 1                                                 RR** 4.05 (2.31; 7.11) (good) for Ascending Colon
Cleansing
(Crude estimate)
* Absolute Risk Difference (Crude)
** Relative Risk (Crude)

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Both active components are locally active in the colon, and neither are absorbed in any detectable amounts.