Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects and in disease states

Taylor, I. W.; Taylor, T.; James, Ian; Doyle, Gerard; Dorf, G; Darragh, A.; Chasseaud, L. F.

doi:10.1007/bf00315147

Cited by 6 publications

(10 citation statements)

References 13 publications

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“…All alterations in pharmacokinetics have been suggested to be related to decreased protein binding and subsequent changes in the volume of distribution and in some cases changes in metabolism of the medication .…”

Section: Methodsmentioning

confidence: 99%

Pain in Chronic Kidney Disease: A Scoping Review

Davison

Koncicki

Brennan

2014

Seminars in Dialysis

141

110

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There is increasing international attention in efforts to integrate palliative care principles, including pain and symptom management, into the care of patients with advanced chronic kidney disease (CKD). The purpose of this scoping review was to determine the extent, range, and nature of research activity around pain in CKD with the goal of (i) identifying gaps in current research knowledge; (ii) guiding future research; and (iii) creating a rich database of literature to serve as a foundation of more detailed reviews in areas where the data are sufficient. This review will specifically address the epidemiology of pain in CKD, analgesic use, pharmacokinetic data of analgesics, and the management of pain in CKD. It will also capture the aspects that pertain to specific pain syndromes in CKD such as peripheral neuropathy, carpal tunnel syndrome, joint pain, and autosomal dominant polycystic kidney disease.

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Section: Methodsmentioning

confidence: 99%

Pain in Chronic Kidney Disease: A Scoping Review

Davison

Koncicki

Brennan

2014

Seminars in Dialysis

141

110

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show abstract

“…The pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects has been evaluated following iv., oral and rectal dosing. The terminal half-life of 1.9 h in healthy subjects was prolonged leading to flip-flop pharmacokinetics in rectal dosing with a half-life of 3.4 h [142]. …”

Section: Drug Examplesmentioning

confidence: 99%

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Yáñez

Remsberg

Sayre

et al. 2011

Therapeutic Delivery

201

108

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Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulation characteristics such as the drug chemical entities themselves or the incorporated excipients can also cause the phenomenon. Yet another contributing factor is the physiological makeup of the extravascular site of administration. In this article, these causes of flip-flop pharmacokinetics are discussed with incorporation of relevant examples and the implications for drug development outlined.

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“…A half-life of this magnitude would lead to negligible accumulation of this drug on the twice-daily dosing regimen which is normally utilised clinically even in the elderly as long as renal function is not severely impaired (Taylor et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Statistical comparison of these data with those of Taylor et al (1991) from younger healthy male subjects showed significantly greater Cmax, AUC and MRT, and longer t½l, in the elderly group (Table 2).…”

Section: Introductionmentioning

confidence: 94%

“…Pharmacokinetic studies of ximoprofen in healthy young subjects and in patients with hepatic or renal disease have also been completed (Taylor et al, 1991 Plasma drug concentrations were measured by a validated procedure involving liquid extraction and gas chromatography with electroncapture detection of the di-pentafluorobenzyl derivative of ximoprofen (the limit of accurate measurement was 0.04 ,ug ml-'). Table 2).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of the anti‐inflammatory drug ximoprofen in healthy young and elderly subjects: comparison with elderly rheumatic patients.

Taylor¹,

Chasseaud²,

Taylor³

et al. 1991

Brit J Clinical Pharma

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The pharmacokinetics of ximoprofen were studied in young and elderly subjects after single and repeated doses up to 30 mg. In healthy elderly subjects (30 mg dose), a mean peak plasma drug concentration of 1.78 micrograms ml‐1 +/‐ 0.83 s.d. occurred at a mean time of 1.95 h +/‐ 1.40 s.d. and, thereafter, concentrations declined monoexponentially with a mean half‐life of 3.8 h +/‐ 1.4 s.d. Comparison of these data with those from younger healthy subjects showed that peak drug concentrations, areas under the curve and half‐lives were about two‐ fold greater in the elderly, these differences probably reflecting a lower systemic drug clearance. Similar results were obtained on comparing data from young healthy subjects and elderly rheumatic patients receiving single and repeated doses of ximoprofen (15 mg twice daily). In patients, the half‐life of ximoprofen was 2.5 h +/‐ 0.7 s.d. Within either group, pharmacokinetic parameters after single or repeated doses were similar: ximoprofen did not accumulate in the plasma of the young or elderly.

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Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects and in disease states

Cited by 6 publications

References 13 publications

Pain in Chronic Kidney Disease: A Scoping Review

Pain in Chronic Kidney Disease: A Scoping Review

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Pharmacokinetics of the anti‐inflammatory drug ximoprofen in healthy young and elderly subjects: comparison with elderly rheumatic patients.

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