Steady state pharmacokinetics and dose equivalents of oral clodronate in renal failure

作者：Makela S^*; Saha H; Ala Houhala I; Liukko Sipi S; Ylitalo P

来源：International Journal of Clinical Pharmacology and Therapeutics, 2011, 49(2): 128-136.

DOI：10.5414/CPP49128

• clodronate
• bisphosphonates
• pharmacokinetics
• renal failure
• oral dosage

Objective: Clodronate is used in the treatment of osteoporosis, and malignancy-associated bone disease. The steady state pharmacokinetics and the dose equivalents of oral clodronate were assessed in subjects with various degrees of renal failure. Materials and methods: 1,600 mg of clodronate was given orally mornings for 11 days to 14 healthy volunteers (creatinine clearance, CL(Cr), > 80 ml/min), and 18, 12 and 16 subjects with mild (50 - 80 ml/min), moderate (30 - 50 ml/min) and severe (< 30 ml/min) renal failure, respectively. Trough drug levels at 4, 7 and 11 days, and concentration-time curves for 72 h after the last dose were followed. Results: In all study groups, the trough drug levels achieved the kinetic steady state within 11 days. The area under the 24-h concentration-time curve (AUC(0-24)) enlarged and the elimination half-life (t(1/2elim)) prolonged progressively when the renal function was impaired. The maximum drug level and the time to maximum were not changed significantly in the renal failure. In the steady state phase, the diurnal drug excretion (E(0-24)) was not changed by the kidney function, but the renal drug clearance (CL(D)) decreased in close correlation with CL(Cr). The normal-to-failed AUC(0-24) ratios in mild, moderate, and severe renal failure were 0.53, 0.43 and 0.31, respectively, when the ideally-matched counterpart was assumed as the normal reference to each renal failure group. Conclusions: In mild, moderate and severe renal failure, 53%, 43% and 31% oral clodronate doses, respectively, resulted in drug AUCs similar to those in controls with normal (> 80 ml/min) CL(CR).

• 出版日期2011-2