Stereoselective disposition of flurbiprofen in healthy subjects following administration of the single enantiomers.

Geißlinger, Gerd; Lötsch, Jörn; Menzel, S.; Kobal, Gerd; Brune, Kay

doi:10.1111/j.1365-2125.1994.tb04295.x

Cited by 53 publications

(45 citation statements)

References 10 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, the mean plasma concentration was 3331 ng ml -1 in the patients receiving orally administered flurbiprofen. This result is comparable with the previous data [9,[11][12][13][14]. Concerning topical application with the same two tapes as used in the present study, it was reported that the Cmax in the plasma was 870 ng ml -1 at the tmax of 11.6 h [8].These data are also comparable with the present result (1369 ng ml -1 ) on the plasma concentration in the patients receiving topically applied flurbiprofen.…”

Section: Discussionsupporting

confidence: 83%

“…After oral administration of a tablet containing 40 mg flurbiprofen, the Cmax in the plasma was 5600 ng ml -1 and the tmax was 1.4 h [9]. After oral administration of a tablet containing 50 mg flurbiprofen, several studies reported that the Cmax ranged from 4200 to 8200 ng ml -1 and that the tmax ranged from 1.3 to 2.8 h [11][12][13][14]. In the present study, the mean plasma concentration was 3331 ng ml -1 in the patients receiving orally administered flurbiprofen.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

Kai

Kondo

Kawaguchi

et al. 2013

Brit J Clinical Pharma

View full text Add to dashboard Cite

AIMTo compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. METHODSixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. RESULTSThe flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P < 0.0330) after topical application (992 ng CONCLUSIONTopical application is an effective method to deliver flurbiprofen to the human body, particularly to soft tissues near the body surface.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

Kai

Kondo

Kawaguchi

et al. 2013

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…This was reported for the antiarrhythmic drug disopyramide [40], in which individual enantiomers yielded R:S enantiomer ratios for Cl and V d of close to 1 when given as individual enantiomers, whereas racemate resulted in R:S ratios of 1.6 and 1.8 for Cl and V d , respectively. Similarly in rat [41], but not in human [42], an enantiomerenantiomer interaction has been noted for the nonsteroidal antiinflammatory drug flurbiprofen, with displacement of R enantiomer by antipode.…”

Section: Distributionmentioning

confidence: 93%

Drug disposition in three dimensions: an update on stereoselectivity in pharmacokinetics

Brocks

2006

Biopharm. Drug Dispos.

134

108

View full text Add to dashboard Cite

Many marketed drugs are chiral and are administered as the racemate, a 50:50 combination of two enantiomers. Pharmacodynamic and pharmacokinetic differences between enantiomers are well documented. Because of enantioselectivity in pharmacokinetics, results of in vitro pharmacodynamic studies involving enantiomers may differ from those in vivo where pharmacokinetic processes will proceed. With respect to pharmacokinetics, disparate plasma concentration vs time curves of enantiomers may result from the pharmacokinetic processes proceeding at different rates for the two enantiomers. At their foundation, pharmacokinetic processes may be enantioselective at the levels of drug absorption, distribution, metabolism and excretion. In some circumstances, one enantiomer can be chemically or biochemically inverted to its antipode in a unidirectional or bidirectional manner. Genetic consideration such as polymorphic drug metabolism and gender, and patient factors such as age, disease state and concomitant drug intake can all play a role in determining the relative plasma concentrations of the enantiomers of a racemic drug. The use of a nonstereoselective assay method for a racemic compound can lead to difficulties in interpretation of data from, for example, bioequivalence or dose/concentration vs effect assessments. In this review data from a number of representative studies involving pharmacokinetics of chiral drugs are presented and discussed.

show abstract

“…However, there is a need to compare (R)-flurbiprofen directly with other non-opioid analgesics like paracetamol or with opioids. Chiral inversion of either (R)-or (S)-flurbiprofen to its optical antipode did not occur to a measurable extent [5]. Thus, the analgesic effects observed after administration of (R)-flurbiprofen have to be attributed to this enantiomer.…”

Section: Discussionmentioning

confidence: 90%

“…The pharmacokinetic parameters of the flurbiprofenenantiomers are published elsewhere [5]. Neither (R)-nor (S)-flurbiprofen was inverted to its optical antipode to a measurable extent.…”

Section: Plasma Concentrations Offlurbiprofenmentioning

confidence: 99%

Effects of flurbiprofen enantiomers on pain‐related chemo‐somatosensory evoked potentials in human subjects.

Lötsch

Geißlinger

Mohammadian

et al. 1995

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

1 The aim of the study was to investigate the analgesic effects of flurbiprofen enantiomers using an experimental pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjective pain ratings. 2 Healthy female volunteers (n = 16, age 23-36 years) participated in a placebocontrolled, randomised, double-blind, four-way crossover study. Single doses of (S)-flurbiprofen (50 mg), (R)-flurbiprofen (50 and 100 mg) and placebo were administered orally. Measurements were taken before and 2 h after administration of the medications. During each measurement, 32 painful stimuli of gaseous carbon dioxide (200 ms duration, interval approximately 30 s) of two concentrations (60 and 65% CO2 v/v) were applied to the right nostril. EEG was recorded from five positions and CSSERP were obtained in response to the painful C02-stimuli. Additionally, subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale (VAS). 3 The CSSERP-amplitude P2, a measure of analgesic effect, decreased after administration of both (R)-and (S)-flurbiprofen, while it increased after placebo. This was statistically significant at recording positions C4 (P < 0.01) and Fz (P < 0.05).The analgesia-related decreases in evoked potential produced by (R)-flurbiprofen were dose-dependent. Comparing similar doses of (R)-and (S)-flurbiprofen, the decrease in CSSERP-amplitudes produced by the (S)-enantiomer was somewhat more pronounced, indicating a higher analgesic potency. 4 The present data indicate that both enantiomers of flurbiprofen produce analgesic effects. Since (R)-flurbiprofen caused only little toxicity in rats as compared with the (S)-enantiomer or the racemic compound, a reduction of the quantitatively most important side effects in the gastrointestinal tract might be achieved by employing (R)-flurbiprofen in pain therapy.

show abstract

Stereoselective disposition of flurbiprofen in healthy subjects following administration of the single enantiomers.

Cited by 53 publications

References 10 publications

Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

Drug disposition in three dimensions: an update on stereoselectivity in pharmacokinetics

Effects of flurbiprofen enantiomers on pain‐related chemo‐somatosensory evoked potentials in human subjects.

Contact Info

Product

Resources

About