Estimated glomerular filtration rate leads to higher drug dose recommendations in the elderly compared with creatinine clearance.

PURPOSE: The elderly are at risk for adverse drug events because of inappropriate dosing of renally eliminated medications. The purpose of this study was to evaluate differences in estimates of kidney function and recommended doses of select medications in the elderly using the Modification of Diet in Renal Disease (MDRD) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with the Cockcroft-Gault (CG) equation. METHODS: Patients 65 years of age and older were included in this retrospective, observational analysis. Kidney function was estimated by CG, MDRD and CKD-EPI equations for all patients and by age category (65-69, 70-79, 80-89 and 90-100 years). Differences in estimates and dosing of allopurinol, enoxaparin, gabapentin, piperacillin/tazobactam and sulfamethoxazole/trimethoprim using the MDRD and CKD-EPI compared with the CG were assessed. RESULTS: In the 4160 patients (98% male, mean age 74 ± 7 years), the MDRD and CKD-EPI estimates were significantly higher than CG estimates for all patients and by age category (p < 0.001). Dosing discordance was predominantly because of a higher dose recommended by MDRD and CKD-EPI estimates compared with CG. Discordance was highest with gabapentin (27%), the medication with the greatest number of dosing stratifications by estimated kidney function, and increased by 66% from the youngest to the oldest age category. CONCLUSIONS: Until newer equations are used uniformly to develop dosing nomograms, it is prudent to adopt a process for drug dosing in the elderly that is more conservative than eGFR based dosing, but that considers the potential for underestimating kidney function with the CG equation.

Alkaline earth complexes of 1,4,7,10-tetrakis(2-hydroxyethyl)- and 1,4,7,10-tetrakis(2-methoxyethyl)-1,4,7,10-tetraazacyclododecane: an equilibrium and kinetic study.

The 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane complexes [M(thec12)]2+, where M2+ = Mg2+, Ca2+, Sr2+, and Ba2+, are characterized by log(K/dm3 mol-1) = 2.86 +/- 0.09, 7.41 +/- 0.04, 6.47 +/- 0.04, and 4.84 +/- 0.03 at 298.2 K in aqueous Et4NClO4 (I = 0.10 mol dm-3), where K is a potentiometrically determined stability constant. The analogous literature values for the 1,4,7,10-tetrakis(2-methoxyethyl)-1,4,7,10-tetraazacyclododecane complexes [M(tmec12)]2+ are 2.47, 5.47, 5.00, and 4.72. The enantiomerization of eight-coordinate delta- and lambda-[M(thec12)]2+ is characterized by k(298.2 K) = 2310 +/- 260, 582 +/- 17, and 445 +/- 5 s-1, delta H++ = 19.1 +/- 0.8, 33.3 +/- 0.5, and 43.9 +/- 0.4 kJ mol-1, and delta S++ = -117 +/- 4, -80.3 +/- 1.8, and -47.0 +/- 1.3 J K-1 mol-1 when M2+ = Mg2+, Ca2+, and Ba2+, respectively, in methanol-12C-d4 as shown by 13C NMR spectroscopy. For the enantiomerization of eight-coordinate delta- and lambda-[M(tmec12)]2+, k(298.2 K) = 310 +/- 1 and 688 +/- 3 s-1, delta H++ = 54.0 +/- 0.2 and 39.6 +/- 0.1 kJ mol-1, and delta S++ = -16.1 +/- 0.5 and -57.9 +/- 0.3 J K-1 mol-1 when M2+ = Ca2+ and Ba2+, respectively. However, [Mg(tmec12)]2+ has a seven-coordinate structure where one of the methoxy groups is not coordinated and exchange of the methoxy groups between the coordinated and free states is characterized by k(298.2 K) = 163,000 +/- 8000 s-1, delta H++ = 35.8 +/- 0.4 kJ mol-1, and delta S++ = -25.1 +/- 1.7 J K-1 mol-1. The intermolecular exchange of thec12 and tmec12 between the coordinated and free states is substantially slower than the enantiomerizations in the first five complexes and the intramolecular exchange process observed in [Mg(tmec12)]2+.