Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics.
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 1/2(S), t 1/2(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 contributing 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.
Chen
C Y
CY
Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Chen
C S
CS
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D003327:Coronary Disease / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism; D006977:Hypertension, Renal / Q000378:metabolism; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013237:Stereoisomerism; D014527:Uric Acid / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014527:Uric Acid; D007052:Ibuprofen