Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group          Peritoneal dialytics, hypertonic solutions ATC code                           B05D B

CAPD 17/18/19 represents a lactate-buffered, glucose-containing electrolyte solution indicated for intraperitoneal administration for the treatment of end-stage renal failure of any origin by continuous ambulatory peritoneal dialysis (CAPD). The calcium dialysis concentration of this peritoneal dialysis solution is set at 1.25 mmol/l, which has been shown to reduce the risk of hypercalcaemia during the concomitant treatment with calcium-containing phosphate binders and/or vitamin D.

The characteristic of continuous ambulatory peritoneal dialysis (CAPD) is the more or less continuous presence of usually 2 litres of dialysis solution in the peritoneal cavity which is replaced by fresh solution three to five times a day.

The basic principle behind every peritoneal dialysis technique is the use of the peritoneum as a semipermeable membrane allowing the exchange of solutes and water between the blood and the dialysis solution by diffusion and convection according to their physico-chemical properties.

The electrolyte profile of the solution is basically the same as that of physiological serum, although it has been adapted (e.g. the potassium content) for use in uraemic patients to enable renal function substitution therapy by means of intraperitoneal substance and fluid exchange. Substances which are normally eliminated with the urine, such as urea, creatinine, inorganic phosphate, uric acid, other solutes and water, are removed from the body into the dialysis solution. It should be borne in mind that medication may also be eliminated during dialysis, and that a dose adjustment may thus be necessary.

Individual parameters (such as patient size, body weight, laboratory parameters, residual renal function, ultrafiltration) must be used to determine the dose and combination of solutions required with differing osmolarity (glucose content), potassium, sodium, and calcium concentrations. The efficacy of therapy should be regularly monitored on the basis of these parameters.

Peritoneal dialysis solutions with a high glucose concentration (2.3% or 4.25%) are used when the body weight is above the desired dry weight. The withdrawal of fluid from the body increases in relation to the glucose concentration of the peritoneal dialysis solution.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Uraemic retention products such as urea, creatinine, and uric acid, inorganic phosphate, and electrolytes such as sodium, potassium, calcium and magnesium are removed from the body into the dialysis solution by diffusion and/or convection.
Dialysate glucose used as an osmotic agent in CAPD 17/18/19 is slowly absorbed decreasing the diffusion gradient between dialysis solution and extracellular fluid. Ultrafiltration is maximal at the beginning of the dwell time reaching a peak after about 2 to 3 hours. Later absorption starts with a progressive loss of ultrafiltrate. After 4 hours the ultrafiltrate averages 100 ml with a 1.5 %, 400 ml with a 2.3 %, and 800 ml with a 4.25 % glucose solution. 60 to 80 % of dialysate glucose are absorbed.
S-lactate used as the buffering agent is almost completely absorbed after a 6-hour dwell time. In patients with a normal hepatic function S-lactate is rapidly metabolised demonstrated by normal values of intermediate metabolites.
Calcium mass transfer depends on the dialysis solution glucose concentration, the effluent volume, the serum ionised calcium, and the calcium concentration in the dialysis solution. The higher the glucose concentration, the effluent volume and the serum ionised calcium concentration, and the lower the calcium concentration in the dialysis solution, the higher is the calcium transfer from the patient to the dialysate. It has been estimated that a typical CAPD schedule of three 1.5% and one       4.25% glucose-containing bags per day would remove up to 160 mg calcium per day enabling a higher intake of oral calcium containing drugs and vitamin D without the risk of hypercalcaemia.