Pharmacokinetics of ketoprofen in the elderly.

Advenier, C.; Roux, A; Gobert, C; Massias, P; Varoquaux, O; Flouvat, B

doi:10.1111/j.1365-2125.1983.tb02145.x

Cited by 83 publications

(21 citation statements)

References 25 publications

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“…Plasma ketoprofen concentrations decreased from the peak with an apparent half-life of about 8.5 h which was not significantly different from the reported terminal half-life in young volunteers (8.3 h). These values which reflect release of drug from the dosage form are considerably longer than the elimination half-life (circa 2 h) of conventionally formulated ketoprofen in volunteers (Lewellen & Templeton, 1976;Stafanger et al, 1981) and elderly patients (Advenier et al, 1983). In one patient (5) on day 1, drug concentrations fell only very slowly from the peak at 5 h. However at times greater than 24 h plasma concentrations will fall more rapidly as drug delivery terminates, so that drug accumulation is not a problem.…”

Section: Resultsmentioning

confidence: 99%

“…Very little free ketoprofen is found in the urine (Upton et al, 1980) although hydrolysis of the glucuronide conjugate 571 occurs upon storage. It has been concluded that a reduction in the rate of metabolic conversion to the ester glucuronide is the cause of reduced elimination of ketoprofen in the elderly (Advenier et al, 1983). There is however no convincing evidence of impaired hepatic function in healthy elderly subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetics of ketoprofen in the elderly have been studied following administration of the conventional formulation (Advenier et al, 1983). The maximum plasma concentration increased by 50% in the elderly and plasma clearance decreased to 50% of that in young volunteers.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

Dennis¹,

Pc²,

Crome³

et al. 1985

Brit J Clinical Pharma

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The pharmacokinetics of ketoprofen following the administration of the first and final dose of a controlled release formulation (200 mg ketoprofen) once daily for 10 days to nine elderly patients have been studied. Plasma ketoprofen concentrations were measured by h.p.l.c. The data were compared to previously reported studies in young male volunteers. Mean +/‐ s.d. peak plasma concentrations (5.6 +/‐ 1.75 micrograms ml‐1 and 6.3 +/‐ 2.7 micrograms ml‐1 on day 1 and day 10, respectively) were higher than those reported in young volunteers given similar treatment, but similar to those reported in young volunteers following 50 mg four times daily of conventionally formulated ketoprofen, and markedly lower than reported following a single 100 mg dose of ketoprofen. The half‐life for drug release (mean +/‐ s.d.) from the controlled release formulation (8.5 +/‐ 7.4 h) and accumulation upon repeated dosing (28%) were essentially the same as reported for young volunteers. The area under the plasma concentration‐time curve was about 65% greater than reported in young volunteers following administration of controlled release ketoprofen. This increase in exposure to ketoprofen is probably partly due to the lower volume of distribution in the elderly and partly due to a reduced renal excretion of the glucuronide metabolite of ketoprofen. It was concluded that controlled release ketoprofen may be administered in standard doses (200 mg once daily) to elderly patients whose elimination processes are not severely impaired (i.e. severe renal failure or hepatic disease).(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

Dennis¹,

Pc²,

Crome³

et al. 1985

Brit J Clinical Pharma

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“…Hence these data ( Figure 3) could be more compelling in support of the conjugate recycling postulate. Previously, it has been suggested that decreased systemic clearance of ketoprofen in elderly subjects is due to a diminished capacity to conjugate the aglycone with glucuronic acid [9]. While declining renal function might be associated with a synchronous impairment of liver function, studies of a number of drugs (forming stable ether glucuronides) administered to patients with renal failure have shown normal glucuronidation capacity [37].…”

Section: Discussionmentioning

confidence: 99%

“…A low percentage of the dose of such drugs is cleared renally in unchanged form yet, paradoxically, a number of them have diminished clearance in patients with renal dysfunction, or in elderly patients in whom renal function is reduced [8][9][10][11][12][13][14]. Moreover, coadministration of probenecid has caused a decrease in the plasma clearance of these NSAIDs [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

The influence of renal function on the enantioselective pharmacokinetics and pharmacodynamics of ketoprofen in patients with rheumatoid arthritis.

Hayball

Nation

Bochner

et al. 1993

Brit J Clinical Pharma

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1 Single oral doses of 100 mg racemic ketoprofen were given to 15 patients (age range:51-79 years) with rheumatoid arthritis and a range of creatinine clearances (CLCR) from 26 to 159 ml min-1. 2 The fractions unbound of (R)-and (S)-ketoprofen in plasma were determined for each subject after in vitro addition of rac-ketoprofen (enantiomer range: 1.00-6.00 ,ug ml-1) to pre-dose plasma. 3 An index of the antiplatelet effect of ketoprofen in vitro was measured as inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood (pre-dose) spiked with rac-ketoprofen. 4 In vivo studies revealed significant associations (P < 0.05) between the reciprocal of AUC for both unbound and total (bound plus unbound) (S)-ketoprofen and CLCR. Corresponding relationships were also observed for the (R)-enantiomer of ketoprofen. In addition, the half-life of each enantiomer was negatively correlated with CLCR.There was a positive relationship between the 24 h urinary recovery of combined non-conjugated and conjugated (R)-ketoprofen and CLCR while that for the (S)-stereoisomer failed to reach statistical significance (P > 0.05). 5 There was no difference between AUC for (R)-and (S)-ketoprofen for either unbound or total drug. 6 The mean ± s.d. percentage unbound of (S)-ketoprofen in plasma (0.801 ± 0.194%) exceeded (P < 0.05) the corresponding value for its optical antipode (0.724 + 0.149%). The percentage unbound of the (S)-enantiomer was higher at 6.00 ,ug ml-l than that at enantiomer concentrations of 3.50 ,ug ml-1 and below, where it was invariant. The percentage unbound of (R)-ketoprofen was independent of plasma concentration up to 6.00 ,ug ml-l. There were no correlations between the percentage unbound of each enantiomer and either serum albumin concentration or CLCR. 7 The relationship between the serum concentration of unbound (S)-ketoprofen and the percentage inhibition of platelet TXB2 generation was described by a sigmoidal Emax equation for each patient. There was no correlation between the unbound concentration of (S)-ketoprofen in serum required to inhibit platelet TXB2 generation by 50% (EC50) and CLCR. The mean ± s.d. EC50 was 0.216 ± 0.143 ng ml-1.8 These data indicate that diminished renal function is associated with an increased exposure to unbound (S)-ketoprofen, presumably due to regeneration of parent aglycone arising from the hydrolysis of accumulated acyl-glucuronide conjugates. The apparent sensitivity of platelet cyclo-oxygenase to the inhibitory effect of (S)-ketoprofen was not influenced by renal function.

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