The effect of concurrent aspirin upon plasma concentrations of tenoxicam.

Day, RO; Paull, Phillip; Lam, S; Swanson, B R; Williams, Kenneth M.; Wade, D. N.

doi:10.1111/j.1365-2125.1988.tb03405.x

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…If it is assumed that the drug is completely absorbed when given orally, clearance values were similar after oral administration (Francis et al 1987;Heinz et al 1988). The mean tY2[3 in healthy volunteers was 60 to 75 hours (Day et al 1987(Day et al , 1988Francis et al 1985;Heintz et al 1984). The tY2[3 of tenoxicam, from both plasma and synovial fluid, were comparable (40 to 50 hours) [Bird et al 1985a;Crevoisier et al 1984].…”

Section: Eliminationmentioning

confidence: 94%

Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

Olkkola

Brunetto

Mattila

1994

Clinical Pharmacokinetics

111

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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: Eliminationmentioning

confidence: 94%

Pharmacokinetics of Oxicam Nonsteroidal Anti-Inflammatory Agents

Olkkola

Brunetto

Mattila

1994

Clinical Pharmacokinetics

111

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“…Steady-state concentrations of aspirin (acetylsalicylic acid) were reported to significantly change pharmacokinetics of tenoxicam after single and multiple doses in healthy volunteers (Day et al 1988a;table XIII). The dose of aspirin was reduced for some study participants to 3.25 or 2.6 g/day.…”

Section: Protein Bindingmentioning

confidence: 98%

“…Repeated doses of tenoxicam were given with aspirin at steady-state and after discontinuation of aspirin. Aspirin (150 mg/L) was shown to compete with tenoxicam (1 to 20 mg/L) for plasma albumin binding sites, creating a significant increase in the unbound concentration of tenoxicam in plasma (0.56 to 1.24%) [Day et al 1988a]. This displacement is thought to be the main reason for the significant increase in tenoxicam elimination when the drug is given with aspirin.…”

Section: Protein Bindingmentioning

confidence: 99%

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Clinical Pharmacokinetics of Tenoxicam

Nilsen

1994

Clinical Pharmacokinetics

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Tenoxicam is a nonsteroidal anti-inflammatory drug (NSAID) in the oxicam group. It is completely absorbed by the oral route and is about 99% protein bound in human plasma. Intake of food delays absorption without affecting bioavailability. There is no evidence for enterohepatic recycling of the drug in humans. Peak plasma concentrations of 2.7 mg/L (range 2.3 to 3.0 mg/L) have been reported in different groups of fasted healthy volunteers 1.9 hours (1.0 to 5.0 hours) after a single oral dose of 20mg. A mean elimination half-life of 67 hours (49 to 81 hours) has been estimated. Tenoxicam demonstrates linear single-dose pharmacokinetics over doses of 10 to 100mg. Because of its low lipophilicity and high degree of ionisation in blood (approximately 99%), the drug is poorly distributed to body tissues and is slowly taken up by hepatic cells. A small apparent volume of distribution of 9.6L (7.5 to 11.5L), and low total plasma clearance of 0.106 L/h (0.079 to 0.142 L/h), have been reported in different groups of healthy volunteers after oral and intravenous administration. Peak concentrations of tenoxicam in synovial fluid are less than one-third of those in plasma and they appear later, 20 hours (10 to 34 hours) after an oral dose. A parallel decrease in synovial fluid and plasma concentrations with time for both total and unbound tenoxicam has been reported. In vivo pH differences between synovial fluid and plasma in patients with rheumatoid arthritis may indicate significantly lower concentrations of unbound ionised tenoxicam in synovial fluid than in plasma. Data on relative binding capacities for tenoxicam in plasma and synovial fluid, and between different groups of individuals, are not conclusive. The protein binding of tenoxicam is pH dependent. The drug is almost entirely eliminated by liver metabolism. The 2 main metabolites, the inactive 5'-hydroxy and 6-O-glucuronidated forms, are excreted in urine and bile, respectively. The existence of additional metabolites in human bile has been suggested. Urinary excretion of the 5'-hydroxy metabolite decreases with reduced renal function. The 5'-hydroxy metabolite is detected in plasma in concentrations 1 to 5% of the parent compound and its decline parallels that of the parent compound (formation-rate limitation). Urinary and faecal excretion of unchanged tenoxicam is less than 1% of the administered dose. No significant amounts of unchanged tenoxicam are excreted in bile. Tenoxicam shows nearly linear pharmacokinetics during multiple-dose administration.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The pharmacokinetics of tenoxicam is independent of patient age [8] or concurrent liver or renal diseases [9]. The effect of concurrent chronic, high dose aspirin therapy generates a decrease of about 24% of the mean half time elimination, and increases of about 49% and 98% of the volume of distribution and clearance, respectively [10]. There is no evidence for entero-hepatic recycling of tenoxicam in humans.…”

Section: Introductionmentioning

confidence: 98%