No effect of diclofenac on the pharmacokinetics of cloxacillin

We studied the influence of diclofenac on the pharmacokinetics of cloxacillin in healthy volunteers, 60 years or older, as well as the possible effect of cloxacillin and diclofenac on urinary protein excretion. In a randomized, double-blind, cross-over study 15 subjects were given 1 g cloxacillin, and placebo or 75 mg diclofenac, as single intravenous doses. Plasma concentrations of cloxacillin were followed over 10.5 hr, and urine excretion of cloxacillin over 24 hr. The effect of the drugs on urinary excretion of protein indicators of glomerular (albumin, IgG) and tubular (protein HC) function was also studied. Total plasma clearance of cloxacillin was with placebo 219 +/- 51 (mean +/- S.D.), and with diclofenac 212 +/- 39 ml/min./1.73 m2 (ns); renal clearance was 97 +/- 21 and 96 +/- 24 ml/min./1.73 m2, respectively (ns). The terminal t1/2 of cloxacillin was 1.03 +/- 0.42 hr with placebo, and 1.12 +/- 0.37 with diclofenac (ns). The mean ratio of AUC0-infinity's (cloxacillin plus diclofenac/cloxacillin plus placebo) was 1.03 (90% CI: 0.99, 1.08). Urinary excretion of the proteins was low and was not increased by cloxacillin or diclofenac. In healthy volunteers, 60 years or older, diclofenac does not alter cloxacillin pharmacokinetics, and neither cloxacillin nor diclofenac in single intravenous doses cause renal dysfunction.