NO EFFECT OF DICLOFENAC ON THE PHARMACOKINETICS OF CLOXACILLIN

We studied the influence of diclofenac on the pharmacokinetics of clox acillin in healthy volunteers, 60 years or older, as well as the possi ble effect of cloxacillin and diclofenac on urinary protein excretion. In a randomized, double-blind, cross-over study 15 subjects were give n 1 g cloxacillin, and placebo or 75 mg diclofenac, as single intraven ous 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 (album in, IgG) and tubular (protein HC) function was also studied. Total pla sma clearance of cloxacillin was with placebo 219+/-51 (mean +/-S.D.), and with diclofenac 212+/-39 ml/min./1.73 m(2) (ns); renal clearance was 97+/-21 and 96+/-24 ml/min./1.73 m(2), respectively (ns). The term inal t(1/2) of cloxacillin was 1.03+/-0.42 hr with placebo, and 1.12+/ -0.37 with diclofenac (ns). The mean ratio of AUC(0-infinity)'s (cloxa cillin plus diclofenac/cloxacillin plus placebo) was 1.03 (90% CI: 0.9 9, 1.08). Urinary excretion of the proteins was low and was not increa sed by cloxacillin or diclofenac. In healthy volunteers. 60 years or o lder, diclofenac does not alter cloxacillin pharmacokinetics, and neit her cloxacillin nor diclofenac in single intravenous doses cause renal dysfunction.