Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics.

Abstract

1 The primary aim of this study was to assess the impact of renal haemodynamics on the pharmacokinetic behaviour of ibuprofen enantiomers. Thirty-two patients and ten age-matched healthy volunteers participated in this study. These patients had at least one of the following risk factors for cardiovascular disorders: hypertension, diabetes mellitus, hyperlipidaemia and hyperuricaemia with or without consequent complications such as coronary artery disease, congestive heart failure, cerebral vascular disease, and chronic renal failure. Renal function in these patients was thus characterized by unstable renal haemodynamics that might render them susceptible to ibuprofen-incurred renal damage. 2 Each subject received a single oral dose of 800 mg of racemic ibuprofen.The pharmacokinetic parameters of (S)-and (R)-ibuprofen, t/2 (S), t1/2(R), AUC(s), AUC(R), V/F(R), and CL/F(R), for each individual were determined from respective plasma concentration-time curves. To assess the effect of individual clinical conditions on the disposition of ibuprofen enantiomers, the arithmetic means of these pharmacokinetic parameters for each disease group were compared with those of the healthy volunteers by a t-test.3 All of these disease groups showed elevated AUC(s) and higher (S)/(R) AUC ratios. These disease states along with gender and age were analyzed by multiple linear regression to discern significant factors for elevating AUC(s). Of these, advanced age (P = 0.02) and hypertension (P = 0.03) were identified as independent factors contributiong to AUC(s) increase in this population. Thus, patients with these two clinical conditions are at particular risk from the adverse renal effect of ibuprofen.

Ibuprofen: pharmacology, efficacy and safety

“…As noted later there are age differences in plasma levels and kinetics of ibuprofen; elderly subjects have slightly prolonged values of elimination half life for the total drug concentrations (Albert and Gernaat 1984) or the AUC for S(?) ibuprofen (Chen and Chen 1995).…”

“…) ibuprofen and higher S(? )/R(-) ratios have been observed in patients with a variety of chronic inflammatory diseases who have impaired renal function (Chen and Chen 1995).…”

Ibuprofen and Paracetamol: Relative Safety in Non-prescription Dosages

“…Differences have, however, been observed in the stereoselective metabolism or elimination of the enantiomers of ibuprofen in patients with pre-existent renal failure after a single dose of 800 mg racemic ibuprofen (Chen & Chen 1994). Metabolism of R(-) to S(+) ibuprofen is accelerated in these subjects and, with reduced renal elimination of the enantiomers, leads to elevated plasma levels of the S(+) form which could promote toxic effects of this drug (Chen & Chen 1994). It has been claimed that ibuprofen pharmacokinetics are not affected in subjects with alcoholic liver disease (Albert & Gernaat 1984), although other studies show that R(-) to S(+) conversion is slowed and elimination prolonged in subjects with cirrhosis.…”

The Effect of Experimental Renal Failure on Tolfenamic Acid Disposition in the Dog

“…2 A critical issue in the use of NSAIDs is their potential toxicity; side or adverse eects may be observed when a dosage regimen which is safe and ecacious in normal subjects is administered to renally impaired patients, as has been recently demonstrated for ibuprofen. 3,4 The advantage of an NSAID of which the disposition is not altered by renal insuciency is evident. It is generally assumed that an NSAID, such as TA, which is mainly cleared by hepatic metabolism is to be preferred when treating patients with a risk of renal failure.…”