Stereoselective disposition of flurbiprofen in normal volunteers.

Knadler, MP; Brater, D. Craig; Hall, S D

doi:10.1111/j.1365-2125.1992.tb04054.x

Cited by 27 publications

(24 citation statements)

References 29 publications

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“…In addition, using rat liver microsomes and human liver microsomes, it was shown that the amount of metabolized (R)-flurbiprofen was greater than the amount of (S)-flurbiprofen, [7,8]. And, faster elimination of the (R)-enantiomer was reported in normal volunteers with the similar distribution volumes of the drug [9]. The observed pharmacokinetic differences between both enantiomers in previous studies reflect the findings in this study.…”

Section: Resultssupporting

confidence: 78%

Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

Uwai

Matsumoto²,

Kawasaki³

et al. 2017

Pharmacology

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Aims: Lithium is administered for treating bipolar disorders and is mainly excreted into urine. Nonsteroidal anti-inflammatory drugs inhibit this process. In this study, we examined the enantioselective effect of flurbiprofen on the disposition of lithium in rats. Methods: Pharmacokinetic experiments with lithium were performed. Results: Until 60 min after the intravenous administration of lithium chloride at 30 mg/kg as a bolus, 17.8% of lithium injected was recovered into the urine. Its renal clearance was calculated to be 1.62 mL/min/kg. Neither creatinine clearance (C_cr) nor pharmacokinetics of lithium was affected by the simultaneous injection of (R)-flurbiprofen at 20 mg/kg. (S)-flurbiprofen impaired the renal function and interfered with the urinary excretion of lithium. The ratio of renal clearance of lithium to C_cr was decreased by the (S)-enantiomer. Conclusion: This study clarified that the (S)-flurbiprofen but not (R)-flurbiprofen inhibited the renal excretion of lithium in rats.

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Section: Resultssupporting

confidence: 78%

Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

Uwai

Matsumoto²,

Kawasaki³

et al. 2017

Pharmacology

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“…Unlike in rats [5,[10][11], kinetic interactions between the isomers of flurbiprofen do not appear to occur to a significant extent in humans as the enantioselective differences following racemate administration [2][3][4] were of the same magnitude as those found in the present study after administration of single enantiomers. In conclusion, flurbiprofen does not undergo gesic may be that it may lack the gastrointestinal toxicity associated with the (S)-enantiomer, as demonstrated in rats [1].…”

Section: Discussionsupporting

confidence: 62%

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

Geißlinger

Lötsch

Menzel

et al. 1994

Brit J Clinical Pharma

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Plasma concentrations of the enantiomers of flurbiprofen were measured following oral administration of (S)-flurbiprofen 50 mg and (R)-flurbiprofen 50 mg and 100 mg to sixteen healthy subjects. Chiral inversion did not occur to a measurable exent. Significantly higher values of AUC (55.2 ± 17.0 vs 44.6 ± 11.2 ig ml-' h) elimination half-life (5.6 ± 1.4 vs 4.0 ± 1.0 h) and mean residence time (7.5 ± 1.6 vs 5.7 ± 1.2 h) were observed after 50 mg (S)-flurbiprofen as compared with 50 mg (R)-flurbiprofen. With the exception of Cmax and AUC values pharmacokinetic data for the 50 mg and the 100 mg dose of (R)-flurbiprofen did not differ significantly. The data are of clinical relevance if (R)-flurbiprofen also has analgesic activity in humans and is to be developed as an analgesic.

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“…Previously, we reported the disposition of R-and Sflurbiprofen in a group of normal volunteers (Knadler et al, 1992). When compared with normal subjects the uraemic patients exhibit significantly greater (P < 0.05) values of oral clearance (R:38.3 ± 12.8 vs 20.4 ± 4.7; S: 30.8 ± 11.5 vs 16.1 ± 3.6 ml min-') and volume of distribution (R: 17.6 ± 3.9 vs 9.1 ± 1.8; S: 14.6 ± 2.5 vs 8.5 ± 1.3 1).…”

Section: Discussionmentioning

confidence: 99%

Stereoselective disposition of flurbiprofen in uraemic patients.

Knadler

Brater

Hall

1992

Brit J Clinical Pharma

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1 Both single and multiple oral doses of 50 mg racemic flurbiprofen were given to eight patients with mild to moderate renal impairment. The plasma and urine concentrations of the R-and S-enantiomers of flurbiprofen and its major metabolites were measured by a stereoselective h.p.l.c. assay. 2 For R-flurbiprofen the oral clearance (mean ± s.d.: 38.3 ± 12.8 vs 30.8 ± 11.5 ml min-1) and volume of distribution (V.; 17.6 ± 3.9 vs 14.6 ± 2.5 1) were significantly greater (P < 0.05) than for the S-enantiomer. A significantly greater (P < 0.05) percent of the dose was excreted in the urine in the R-configuration (16.4 ± 6.0 vs 10.9 ± 4.2%). 3 Plasma protein binding of the enantiomers of flurbiprofen was determined by ultrafiltration. The unbound clearance and unbound V, were not different between enantiomers consistent with the (not significantly) greater percent unbound of Rflurbiprofen (0.079 ± 0.014%) vs S-flurbiprofen (0.064 ± 0.015%). 4 Relative to normal volunteers, the uraemic subjects exhibited a significantly greater (P < 0.05) oral clearance, V, and percent unbound for both enantiomers; unbound clearance and unbound V, did not differ from healthy controls.5 The disposition of flurbiprofen enantiomers was not changed upon multiple dosing and no evidence of futile cycling was found. Adjustment of flurbiprofen dosing rate in uraemic subjects is not indicated on the basis of pharmacokinetics.

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Stereoselective disposition of flurbiprofen in normal volunteers.

Cited by 27 publications

References 29 publications

Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

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

Stereoselective disposition of flurbiprofen in uraemic patients.

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