Single-dose and steady-state pharmacokinetics of piroxicam in elderly vs young adults

Darragh, A.; Gordon, Arnold J.; O'Byrne, H.; Hobbs, Donald C.; Casey, Eoin

doi:10.1007/bf00543328

Cited by 36 publications

(11 citation statements)

References 14 publications

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“…Thus, it is not surprising that its apparent oral volume of distribution is only 0.10 to 0.20 L/kg (Darragh et al 1985;Kobayashi et al 1984;Richardson et al 1985Richardson et al , 1986Woolf et al 1983). Since piroxicam has not been administered to humans intravenously, volume of distribution was determined after oral administration, assuming complete absorption.…”

Section: Distributionmentioning

confidence: 94%

“…Renal impairment does not appear to alter the pharmacokinetic profile of piroxicam (Darragh et al 1985;Dupont et al 1982;Woolf et al 1983). Interestingly, and in accordance with pharmacokinetic theory, the elimination of piroxicam, a low extraction drug, is enhanced in patients with endstage renal disease.…”

Section: Effect Of Age and Diseasementioning

confidence: 96%

“…The pharmacokinetic profile of piroxicam appears to be independent of age (Darragh et al 1985;Edwards et al 1985;Woolf et al 1983). Richardson et al (1985) have reported that elderly healthy women eliminate piroxicam at a slower rate than young healthy women.…”

Section: Effect Of Age and Diseasementioning

confidence: 97%

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Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

Olkkola

Brunetto

Mattila

1994

Clinical Pharmacokinetics

110

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Oxicam nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of structurally closely related substances with anti-inflammatory, analgesic and antipyretic activities. They have a weakly acidic character and are extensively bound to plasma proteins. Piroxicam, the most widely used oxicam, is well absorbed after oral administration. Peak plasma concentrations (Cmax) of the drug are reached within 2 to 4 hours. Piroxicam has a small volume of distribution and a low plasma clearance. It undergoes hepatic metabolism and only 5 to 10% is excreted unchanged in urine. The elimination half-life varies between 30 and 70 hours. Age of the patient and renal or hepatic dysfunction do not seem to have any major effect on the pharmacokinetics of piroxicam. The drug reduces the renal excretion of lithium to a clinically significant extent, but the clinical significance of piroxicam-aspirin (acetylsalicylic-acid) and piroxicam-acenocoumarol interaction has not been established. Ampiroxicam, droxicam and pivoxicam are prodrugs of piroxicam that have been synthesised to reduce piroxicam-related gastrointestinal irritation. All prodrugs are well absorbed, but Cmax values are reached later than those following administration of piroxicam. Tenoxicam is used in the management of rheumatic and inflammatory diseases. Mean Cmax values are achieved 2 hours postdose. Food reduces the rate but not the extent of absorption. The oral bioavailability of tenoxicam is 100% and rectal bioavailability is 80%. Like piroxicam, tenoxicam has a low volume of distribution and low plasma clearance. It is eliminated through hepatic metabolism. The mean elimination half-life is 60 to 75 hours. The pharmacokinetics of tenoxicam are independent of patient age, or concurrent liver or renal diseases. High doses of aspirin have been shown to increase the elimination of tenoxicam, but this has little clinical significance. Isoxicam was in widespread clinical use until its worldwide marketing was suspended because of fatal skin reactions. Isoxicam is completely absorbed, but Cmax values are not reached until 10 hours postdose. It has a low plasma clearance, approximately 5 ml/min (0.3 L/h), and low volume of distribution. The mean elimination half-life is 30 hours and does not appear to be affected by the age of the patient. Isoxicam potentiated the anticoagulant effect of warfarin, necessitating a 20% dosage reduction. Lornoxicam differs from other oxicam NSAIDs because it has a short elimination half-life of 3 to 4 hours. On the basis of limited data, some individuals seem to eliminate lornoxicam very slowly, suggesting the presence of polymorphic metabolism. The pharmacokinetics of cinnoxicam and sudoxicam have not been studied thoroughly.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Distributionmentioning

confidence: 94%

Section: Effect Of Age and Diseasementioning

confidence: 96%

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Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

Olkkola

Brunetto

Mattila

1994

Clinical Pharmacokinetics

110

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“…No significant differences were observed when steady-state plasma concentrations were compared in 26 subjects with normal renal function and 18 patients with mild to moderate renal impairment (Darragh et al 1985), and the tIl> did not change whatever the degree of renal failure (Woolf et al 1983). Piroxicam is widely used: one advantage is its long half-life, leading to improved efficacy and patient compliance.…”

Section: Piroxicammentioning

confidence: 97%

Pharmacokinetics of Newer Drugs in Patients with Renal Impairment (Part I)

Fillastre

Singlas

1991

Clinical Pharmacokinetics

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Many drugs are eliminated via the renal route and the usual dose must be modified in patients with severe renal impairment. This review is an attempt to supply physicians with the more recent data on pharmacokinetic studies of new drugs administered in uraemic patients. The review is in 2 parts: the first indicates the results of studies on the pharmacokinetics of antibiotic agents, antifungal, antiviral and antiulcer drugs, and nonsteroidal anti-inflammatory drugs. Special mention is made of epoetin (recombinant human erythropoietin). It was not possible to give all the information collected from the recent literature: since mild renal failure has little effect on the fate of a drug, pharmacokinetic data obtained in patients with a creatinine clearance (CLCR) of more than 50 ml/min has been omitted. Both the text and tables give recommendations for treating patients with moderate renal insufficiency (CLCR of about 50 ml/min), more severe renal impairment (CLCR between 10 and 50 ml/min) and end-stage renal failure with a very low creatinine clearance (below 10 ml/min). It was not possible to give uniform recommendations (i.e. reducing the dose while maintaining the same interval, or giving the same dose and prolonging the interval). This article follows the recommendations of the authors, which may vary for drugs in similar classes.

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“…It is noteworthy that after treatment with piroxicam is stopped the active drug remains in the circulation for several days, or perhaps longer in the elderly. 9 Regardless of the relative risks ofanti-inflammatory drugs, we have treated 23 patients with serious peptic ulcer complications related to piroxicam over three years. Moreover, nine of these complications were fatal.…”

mentioning

confidence: 99%

Ulcerogenicity of piroxicam: an analysis of spontaneously reported data

Calin¹

1987

BMJ

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Single-dose and steady-state pharmacokinetics of piroxicam in elderly vs young adults

Cited by 36 publications

References 14 publications

Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

Pharmacokinetics of Newer Drugs in Patients with Renal Impairment (Part I)

Ulcerogenicity of piroxicam: an analysis of spontaneously reported data

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