Comparative pharmacology of s(+)- ibuprofen and (RS)- ibuprofen
Date
2001
Authors
Evans, A.M.
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Journal article
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Clinical Rheumatology, 2001; 20(1S):9-14
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Abstract
Racemic ibuprofen, which contains equal quantities of R(-)-ibuprofen and S(+)-ibuprofen, has been used as an anti-inflammatory and analgesic agent for over 30 years. Although the S(+)-enantiomer is capable of inhibiting cyclooxygenase (COX) at clinically relevant concentrations, R(-)-ibuprofen is not a COX inhibitor. The two enantiomers of ibuprofen are therefore different in terms of their pharmacological properties and may be regarded as two different ‘drugs’. They also differ in terms of their metabolic profiles. For example, R(-)-ibuprofen becomes involved in pathways of lipid metabolism and is incorporated into triglycerides along with endogenous fatty acids. S(+)-Ibuprofen does not appear to become involved in these unusual metabolic reactions, which is why S(+)-ibuprofen is regarded as being metabolically ‘cleaner’ than racemic ibuprofen. When racemic ibuprofen is given to humans, a substantial fraction of the dose of R(-)-ibuprofen (50%-60%) undergoes ‘metabolic inversion’ to yield S(+)-ibuprofen. On this basis, it has been argued that to obtain clinical effects that are comparable to those of a given dose of racemic ibuprofen, the dose of S(+)-ibuprofen would need to be about 75% of the dose of the racemate. However, this ‘pharmacokinetic’ rationale does not take into account the fact that inversion is not instantaneous, that there is variability in the extent of inversion between individuals, and that the kinetics of inversion may differ depending on the dosing situations.
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Copyright 2001 Clinical Rheumatology