Caspofungin is slowly metabolized by hydrolysis and N-acetylation of the peptide compound to form an open ring. At a later time (after 5 or more days after administration of a parabolan single dose of labeled [ 3 H] caspofungin acetate) indicated in plasma is low (less than 7 pmol / mg protein or less, or 1.3% of the administered dose) covalently associated with a protein labeled [ 3 H] caspofungin acetate, due to the formation of two active intermediates caspofungin decomposition.
In the ensuing metabolic process, including hydrolysis to constituent amino acids and their derivatives, and digidroksitomotirozina to form N-acetyl digidroksigomotirozina. These derivatives exhibit only tyrosine in urine, which indicates the high renal clearance of these metabolites.
of excretion undergoes about 75% of the drug (pharmacokinetic study with radiolabeled caspofungin): 41% in urine and 34% in feces.
Plasma concentrations of caspofungin and labels within the first 24-48 hours after dosing did not differ, then the drug concentration decreases faster with the decrease of its concentration below the quantification is observed 6-8 days after dosing, and radiolabelling – after 22.3 weeks. A small amount of caspofungin is excreted unchanged in the urine (approximately 1.4% of the dose).
Renal clearance of parent drug is low and amounts to about 0.15 ml / min.
The pharmacokinetic characteristics of certain groups of patients
, depending on gender
concentration in plasma parabolan caspofungin in healthy men and women in the 1 st day after administration of a single dose of 70 mg of the same. After 13 daily injections of 50 mg of the concentration of caspofungin in plasma, some women was about 20% higher than in men. Older content of caspofungin in the blood plasma of healthy male and female elderly (65 years or older) above 28% (estimate in terms of the area under the curve, “concentration-time» – AUC) compared with healthy young men. Elderly patients with invasive candidiasis or background were observed empirical therapy such as moderate changes in the plasma concentration of the drug, as in a group of healthy elderly patients compared with healthy young patients. Correction of dosage regimen for the elderly (65 years or older) patients is not required. In patients with liver function impairment concentration of caspofungin in plasma of patients with mild hepatic insufficiency (5- 6 points on a scale Child-Pugh) after administration of a single dose of 70 mg increases by about 55% (AUC) compared to healthy individuals. Introduction of the drug in these patients for 14 days (70 mg on day 1, followed by daily administration of 50 mg) was accompanied by an increase in the plasma concentration of caspofungin at 19-25% (AUC) on days 7 and 14 compared with healthy volunteers. Children A five long-term clinical studies with the study drug Cancidas ® in patients under 18 years, including pharmacokinetics study (initial study in adolescents [12-17] and children [2-11 years], and then – in young children [3-23 months ] and in infants and children, the first three months of life). in adolescents (12-17 years) treated with caspofungin 50 mg / m 2 (maximum daily dose – 70 mg), the blood plasma concentration (AUC h ) generally corresponds to a concentration in adults treated with caspofungin 50 mg per day. All teenagers caspofungin obtained above at a dose of 50 mg, and six out of eight patients received a maximum daily dose of 70 mg. Plasma concentration of caspofungin in these patients was lower compared to the concentration in adults treated with the drug in a daily dose of 70 mg, the dose is one which is most often administered to adolescents. In children aged 2-11 years, caspofungin receiving 50 mg / m 2 per day (maximum daily dose of 70 mg per day), his plasma concentration (AUC 0-24 ) was comparable with that of adult patients treated with caspofungin 50 mg per day. The first day of administration of the drug concentration in plasma (AUC 0-24 ) was slightly higher in children than adults (37% compared with doses of 50 mg / m 2 and 50 mg once a day).However, it should be emphasized that the plasma concentration (AUC 0-24 ) in children on the first day was still lower than in adults with chronic treatment. In children aged 3-23 months, which caspofungin administered in a daily dose of 50 mg / m 2 (maximum dose – 70 mg), caspofungin plasma concentrations after prolonged use has been comparable with the concentration in adults who are prescribed dose of 50 mg / day. As with older children, the children of this age group in the caspofungin receiving 50 mg / m 2 , the drug concentration in plasma was higher in the first day of treatment compared with adults who received a standard dose of 50 mg of caspofungin. Pharmacokinetic parameters of caspofungin at 50 mg / m 2 in children of younger age group (3-23 months) and older groups (2-11 years) with the same dosing regimen were comparable. In infants and children up to 3 months, which was administered in the caspofungin 25 mg / m 2 , caspofungin peak concentration (C 1h ) and the threshold concentration (C24H ), after parabolan repeated injections of the same indices correspond to adults receiving the drug at 50 mg per day. On the first day of the peak concentration of C 1h it was comparable to adults, and the threshold concentration of C 24h was moderately increased in newborns and infants compared with those of adults. Determination of plasma drug concentration (AUC 0-24 ) was conducted in this study because of sampling difficulties. It should be noted that the study of the efficacy and safety in the prospective clinical studies of adequate drug in infants and children up to 3 months was conducted. linda durbesson before and after