pproximately 70% of the radiolabeled dose is recovered in the feces and 18% is recovered in the urine. In healthy subjects, the mean elimination half-life of paricalcitol is 4 to 6 hours over the studied dose range of 0.06 to 0.48 mcg/kg. The pharmacokinetics of paricalcitol capsule have been studied in patients with chronic kidney disease (CKD) Stage 3 and 4 patients. After administration of 4 mcg paricalcitol capsule in CKD Stage 3 patients, the mean elimination half-life of paricalcitol is 17 hours. The mean half-life of paricalcitol is 20 hours in CKD Stage 4 patients when given 3 mcg of paricalcitol capsule.
Table 1. Paricalcitol Capsule Pharmacokinetic Characteristics in CKD Stage 3 and 4 Patients Pharmacokinetic Parameters CKD Stage 3
n = 15* CKD Stage 4
n = 14*
* Four mcg paricalcitol capsule was given to CKD Stage 3 patients; three mcg paricalcitol capsule was given to CKD Stage 4 patients.
Cmax (ng/mL) 0.11 ± 0.04 0.06 ± 0.01
AUC0-∞ (ng•h/mL) 2.42 ± 0.61 2.13 ± 0.73
CL/F (L/h) 1.77 ± 0.50 1.52 ± 0.36
V/F (L) 43.7 ± 14.4 46.4 ± 12.4
t1/2 16.8 ± 2.65 19.7 ± 7.2
Special Populations
Geriatric
The pharmacokinetics of paricalcitol have not been investigated in geriatric patients greater than 65 years (see PRECAUTIONS).
Pediatric
The pharmacokinetics of paricalcitol have not been investigated in patients less than 18 years of age.
Gender
The pharmacokinetics of paricalcitol following single doses over 0.06 to 0.48 mcg/kg dose range were gender independent.
Hepatic Impairment
The disposition of paricalcitol (0.24 mcg/kg) was compared in patients with mild (n = 5) and moderate (n = 5) hepatic impairment (as indicated by the Child-Pugh method) and subjects with normal hepatic function (n = 10). The pharmacokinetics of unbound paricalcitol were similar across the range of hepatic function eva luated in this study. No dosing adjustment is required in patients with mild and moderate hepatic impairment. The influence of severe hepatic impairment on the pharmacokinetics of paricalcitol has not been eva luated.
Renal Impairment
Following administration of Zemplar Capsules, the pharmacokinetic profile of paricalcitol for CKD Stage 5 on hemodialysis (HD) or peritoneal dialysis (PD) was comparable to that in CKD 3 or 4 patients. Therefore, no special dosing adjustments are required other than those recommended in the Dosage and Administration section (see DOSAGE AND ADMINISTRATION).
Drug Interactions
An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL) (approximately 20-fold greater than that obtained after highest tested dose). In fresh primary cultured hepatocytes, the induction observed at paricalcitol concentrations up to 50 nM was less than two-fold for CYP2B6, CYP2C9 or CYP3A, where the positive controls rendered a six- to nineteen-fold induction. Hence, paricalcitol is not expected to inhibit or induce the clearance of drugs metabolized by these enzymes.
Omeprazole
The pharmacokinetic interaction between paricalcitol capsule (16 mcg) and omeprazole (40 mg; oral) was investigated in a single dose, crossover study in healthy subjects. The pharmacokinetics of paricalcitol were unaffected when omeprazole was administered approximately 2 hours prior to the paricalcitol dose.
Ketoconazole
The effect |
