Disposition of Ibuprofen in Patients with Liver Cirrhosis

Li, Gao; Treiber, Gerhard; Maier, Karlernst; Walker, S.; Klotz, Ulrich

doi:10.2165/00003088-199325020-00008

Cited by 26 publications

(13 citation statements)

References 27 publications

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“…reported to be independent of the dose of racemic ibuprofen [37]. This consistency of the reported values of F i in healthy volunteers justi®es its use from the literature, unless data originate from subjects with liver disease where inversion is impaired [21], or when subjects were treated with clo®brate that increases the inversion of R-to S-ibuprofen [23]. The model presented here may also be used when direct information on S-ibuprofen pharmacokinetics is available from concomitant administration of labelled S-ibuprofen, making it possible directly to estimate F i rather than incorporating a value from the literature.…”

Section: Discussionsupporting

confidence: 61%

“…A fraction F i of the clearance of R-ibuprofen consists of inversion clearance of R-to S-ibuprofen, CL R, inv . The inversion was assigned to the central compartments what is compatible with the fact that most of the inversion takes place in the liver [20] while other sites play a minor role [21,22]. The fraction F i was set to 0.6 as reported from a previous study in a comparable study population [23].…”

Section: Discussionmentioning

confidence: 99%

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Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate

Lötsch

Muth-Selbach

Tegeder

et al. 2001

Br J Clin Pharmacol

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Aims To assess the pharmacokinetic equivalence of two different formulations of ibuprofen lysinate with special focus on the expected effects. Methods Sixteen healthy volunteers received cross-over ibuprofen lysinate as either one tablet of 400 mg (`test') or two tablets of 200 mg (`reference'). Ibuprofen plasma concentrations were followed up for 10 h. Bioequivalence was assessed by standard noncompartmental methods. Ibuprofen plasma concentrations were ®tted with a model that took bioinversion of R-to S-ibuprofen into account. Results Peak plasma concentrations of R-and S-ibuprofen were 18. (reference). A speci®c plasma concentration was reached with the test formulation about 5 min later than with the reference. Parameters from compartmental modelling were (given for R-and then for S-ibuprofen): body clearance: 4.9 and 4.64 l h x1 , central volume of distribution: 2.8 and 4.1 l, intercompartment clearance: 5.1 and 5.45 l h x1 , peripheral volume of distribution: 4.1 and 5.2 l. The absorption rate constant was 1.52 h x1 , and the test but not the reference formulation had a lag time of 0.1 h. Simulations showed similarity between formulations of the expected effects except for a calculated delay of 6 min with the test formulation. Conclusions Ibuprofen formulations were bioequivalent. The pharmacokinetic model may serve as a basis for future pharmacokinetic/pharmacodynamic calculations after administration of racemic ibuprofen.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate

Lötsch

Muth-Selbach

Tegeder

et al. 2001

Br J Clin Pharmacol

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“…ibuprofen with evidence of reduced metabolic inversion of the R(-) to S(?) enantiomer (Li et al 1993). Alcoholic liver disease also prolongs the T max for the total Cp as well as the t 1/2 (Albert and Gernaat 1984).…”

Section: Pharmacokinetics In Adultsmentioning

confidence: 99%

Ibuprofen: pharmacology, efficacy and safety

2009

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This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine-imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.

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“…Results from previous studies have showed that the (S)/(R) AUC ratio varies in different pathological conditions. The reported values for renal failure [8] and liver cirrhosis [17] were 2.1 and 0.91, respectively, which may be accounted for by the roles of liver and kidney in the disposition of ibuprofen enantiomers (Figure 2). …”

Section: Discussionmentioning

confidence: 98%

Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics.

Chen

1995

Brit J Clinical Pharma

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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.

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Disposition of Ibuprofen in Patients with Liver Cirrhosis

Cited by 26 publications

References 27 publications

Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate

Simultaneous fitting of R- and S-ibuprofen plasma concentrations after oral administration of the racemate

Ibuprofen: pharmacology, efficacy and safety

Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics.

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