TY - JOUR
T1 - Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function
AU - Takimoto, Chris H.
AU - Graham, Martin A.
AU - Lockwood, Graham
AU - Ng, Chee M.
AU - Goetz, Andrew
AU - Greenslade, Dennis
AU - Remick, Scot C.
AU - Sharma, Sunil
AU - Mani, Sridhar
AU - Ramanathan, Ramesh K.
AU - Synold, Timothy W.
AU - Doroshow, James H.
AU - Hamilton, Anne
AU - Mulkerin, Daniel L.
AU - Ivy, Percy
AU - Egorin, Merrill J.
AU - Grem, Jean L.
PY - 2007/8/15
Y1 - 2007/8/15
N2 - Purpose: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. Experimental Design: Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, ≥60 mL/min), B (mild, CrCL, 40-59mL/min), C (moderate, CrCL, 20-39mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinumin plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2. Results: Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the β-half-life was significantly prolonged by renal impairment, with values of 14.0 ± 4.3, 20.3 ± 17.7, 29.2 ± 29.6, and 68.1h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m 2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 ± 5.03, 39.7 ± 11.5, and 44.6 ± 14.6 Ag μh/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min). Conclusions: Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.
AB - Purpose: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. Experimental Design: Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, ≥60 mL/min), B (mild, CrCL, 40-59mL/min), C (moderate, CrCL, 20-39mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinumin plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2. Results: Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the β-half-life was significantly prolonged by renal impairment, with values of 14.0 ± 4.3, 20.3 ± 17.7, 29.2 ± 29.6, and 68.1h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m 2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 ± 5.03, 39.7 ± 11.5, and 44.6 ± 14.6 Ag μh/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min). Conclusions: Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.
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U2 - 10.1158/1078-0432.CCR-07-0475
DO - 10.1158/1078-0432.CCR-07-0475
M3 - Article
C2 - 17699862
AN - SCOPUS:34548059736
SN - 1078-0432
VL - 13
SP - 4832
EP - 4839
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -