Meloxicam, 15 mg/day, spares platelet function in healthy volunteers*1

DEMEIJER, A

doi:10.1053/cp.1999.v66.a101063

Cited by 52 publications

(31 citation statements)

References 27 publications

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“…In the present study, a 47% increase in the exposure to meloxicam by voriconazole was not associated with increased COX-1 inhibition. The maximum decline of the synthesis of TxB 2 was 56 and 49% in the control and voriconazole phases, respectively, which is comparable with other studies, in which TxB 2 synthesis was inhibited 35 to 66% by 15 mg of meloxicam (7,19,22). Accordingly, it is unlikely that a shortterm concomitant use of voriconazole or other CYP2C9 inhibitors with meloxicam would increase its risk for gastrointestinal adverse effects or bleeding.…”

Section: Discussionsupporting

confidence: 86%

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

Hynninen

Olkkola

Kurkinen

et al. 2009

Antimicrob Agents Chemother

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This study investigated the effect of voriconazole, an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4, and itraconazole, an inhibitor of CYP3A4, on the pharmacokinetics and pharmacodynamics of meloxicam. Twelve healthy volunteers in a crossover study ingested 15 mg of meloxicam without pretreatment (control), after voriconazole pretreatment, and after itraconazole pretreatment. The plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B 2 (TxB 2 ) generation were monitored. Compared to the control phase, voriconazole increased the mean area under the plasma concentration-time curve from 0 to 72 h (AUC 0-72 ) of meloxicam by 47% (P < 0.001) and prolonged its mean half-life (t 1/2 ) by 51% (P < 0.01), without affecting its mean peak concentration (C max ). In contrast, itraconazole decreased the mean AUC 0-72 and C max of meloxicam by 37% (P < 0.001) and by 64% (P < 0.001), respectively, and prolonged its t 1/2 and time to C max . The plasma protein unbound fraction of meloxicam was unchanged by voriconazole and itraconazole. Lowered plasma meloxicam concentrations during the itraconazole phase were associated with decreased pharmacodymic effects of meloxicam, as observed by weaker inhibition of TxB 2 synthesis compared to the control and voriconazole phases. Voriconazole increases plasma concentrations of meloxicam, whereas itraconazole, unexpectedly, decreases plasma meloxicam concentrations, possibly by impairing its absorption.Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with selectivity toward cyclo-oxygenase 2 (COX-2) compared to 19). It is widely used in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other rheumatological conditions. Meloxicam has an oral bioavailability of 89%, and its maximum plasma concentrations (C max ) are achieved within 4 to 11 h (10, 26). It is extensively bound to plasma proteins (Ͼ99%), mainly to albumin (24). The elimination half-life (t 1/2 ) of meloxicam ranges from 13 to 20 h, and it is suitable for once-daily dosing (24,26). Meloxicam is extensively metabolized in the liver, primarily by polymorphic cytochrome P450 2C9 (CYP2C9) enzyme, and to a minor extent by CYP3A4 enzyme, to four pharmacologically inactive metabolites (6, 24). Only negligible amounts of the parent drug are found in urine and in feces (24). The effect of different genotypes on the pharmacokinetics of meloxicam is not known.Voriconazole is a triazole antifungal agent used both intravenously and orally to treat invasive fungal infections. Voriconazole undergoes extensive oxidative metabolism involving CYP enzymes CYP2C19, CYP2C9, and CYP3A4 (13). Voriconazole is also an inhibitor of CYP2C9, CYP3A4, and CYP2C19 catalyzed reactions both in vitro and in vivo (17,21,23,25). Another triazole antifungal, itraconazole, is a potent inhibitor of CYP3A4 (18, 28), but it is without effect on CYP2C9 in humans (15,27).Because both voriconazole and itraconazole inhibit CYP enzymes involved in the metabolism of meloxicam, ...

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Section: Discussionsupporting

confidence: 86%

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

Hynninen

Olkkola

Kurkinen

et al. 2009

Antimicrob Agents Chemother

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“…Meloxicam was also more potent in reducing edema of the inflamed rat paw than indomethacin, piroxicam, diclofenac, or naproxen (Engelhardt et al, 1995;Engelhardt, 1996) and produced analgesia in rat and dog models of inflammatory pain (Cross et al, 1997;Laird et al, 1997;Santos et al, 1998). At therapeutic doses of 7.5 or 15 mg, meloxicam did not reduce platelet aggregation or prolong bleeding time ex vivo (Stichtenoth et al, 1997;De Meijer et al, 1999;Panara et al, 1999;Tegeder et al, 1999), although thromboxane formation by platelets was inhibited by 35% after 15 mg of meloxicam. This demonstrated the low inhibitory activity against COX-1 of meloxicam in vivo.…”

Section: A Treatment Of Inflammatory Diseasesmentioning

confidence: 99%

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

2004

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“…Children with a megarectum may not sense the faecal matter in the rectum, and have diminished urgency to defecate 4,5 , which may lead to faecal soiling. It is important to distinguish this involuntary soiling from encopresis, in which the child voluntarily passes normal stools in unacceptable places.…”

Section: Introductionmentioning

confidence: 99%

Warfarin, antiplatelet drugs and their interactions

Ho¹,

Brighton²

2002

Aust Prescr

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SYNOPSISPatients who are being treated with warfarin may sometimes be prescribed or buy antiplatelet drugs, such as aspirin. As warfarin and antiplatelet drugs increase the risk of bleeding, their combination can put patients at risk of a major haemorrhage. This risk may be further increased by the patient's age and other illnesses. A thorough history is therefore important in assessing the risk of haemorrhage. Patients need to be informed of the risk and should be encouraged to have their international normalised ratio checked regularly.

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Meloxicam, 15 mg/day, spares platelet function in healthy volunteers*1

Abstract: Meloxicam, 15 mg/day caused a major reduction of maximum thromboxane production but no reduction in collagen- or arachidonic acid-induced platelet aggregation and only minor increase of the closure time.

Cited by 52 publications

References 27 publications

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition

Warfarin, antiplatelet drugs and their interactions

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