Pharmacokinetics of Oxicam Nonsteroidal

Anti-Inflammatory Agents
Dr Klaus T. Olkkola,
Aurora V. Brunetto,
Mauri J. Mattila

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Summary
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 C max 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. However, like other
oxicams, they appear to be absorbed completely after oral administration. Although the development of sudoxicam
was stopped because of frequent adverse effects, this drug is interesting because, unlike other oxicams, its appears to
have nonlinear elimination pharmacokinetics.

http://www.ncbi.nlm.nih.gov/pubmed/8162655

Oxicam obat anti-inflammatory drugs (NSAIDs) adalah kelompok zat struktural terkait erat
dengan anti-inflamasi, analgesik dan antipiretik kegiatan. Mereka memiliki karakter asam lemah
dan secara luas terikat pada protein plasma. Piroksikam, yang oxicam yang paling banyak
digunakan, baik diserap setelah pemberian oral. Konsentrasi plasma puncak (Cmax) dari obat
yang dicapai dalam 2 sampai 4 jam. Piroksikam memiliki volume kecil distribusi dan clearance
plasma rendah. Itu mengalami metabolisme hati dan hanya 5 sampai 10% diekskresikan tidak
berubah dalam urin. Penghapusan paruh bervariasi antara 30 dan 70 jam. Usia pasien dan
disfungsi ginjal atau hati tampaknya tidak memiliki pengaruh besar terhadap farmakokinetika
piroksikam. Obat mengurangi ekskresi ginjal litium sampai batas yang signifikan secara klinis,
tetapi arti klinis piroksikam-aspirin (asetilsalisilat asam) dan interaksi piroksikam-
acenocoumarol belum ditetapkan. Ampiroxicam, droxicam dan pivoxicam adalah prodrugs
piroksikam yang telah disintesis untuk mengurangi-piroksikam terkait iritasi gastrointestinal.
Semua prodrugs diserap dengan baik, tetapi nilai-nilai Cmax dicapai paling lambat mereka
setelah pemberian piroksikam. Tenoxicam digunakan dalam pengelolaan penyakit rematik dan
radang. Nilai rata-rata yang dicapai Cmax 2 jam postdose. Makanan mengurangi tingkat tapi
tidak tingkat penyerapan. Bioavailabilitas oral tenoxicam adalah 100% dan bioavailabilitas dubur
adalah 80%. Seperti piroksikam, tenoxicam memiliki volume yang rendah distribusi dan
pembersihan plasma yang rendah. Hal ini dieliminasi melalui metabolisme hati. Mean paruh
eliminasi adalah 60 sampai 75 jam. Farmakokinetik tenoxicam independen dari usia pasien, atau
hati atau penyakit ginjal bersamaan. Dosis tinggi aspirin telah terbukti meningkatkan
penghapusan tenoxicam, tapi ini memiliki sedikit signifikansi klinis. Isoxicam dalam
penggunaan klinis luas sampai pemasaran di seluruh dunia dihentikan karena reaksi kulit yang
fatal. Isoxicam benar-benar diserap, tetapi nilai-nilai Cmax tidak tercapai sampai 10 jam
postdose. Memiliki izin plasma yang rendah, sekitar 5 ml / menit (0,3 L / h), dan volume yang
rendah distribusi. Mean paruh eliminasi adalah 30 jam dan tidak tampaknya dipengaruhi oleh
usia pasien. Isoxicam potentiated efek antikoagulan warfarin, memerlukan pengurangan dosis
20%. Lornoxicam berbeda dari NSAID oxicam lainnya karena memiliki eliminasi pendek paruh
3 sampai 4 jam. Berdasarkan data yang terbatas, beberapa orang tampaknya untuk
menghilangkan lornoxicam sangat lambat, menunjukkan adanya metabolisme polimorfik.
Farmakokinetik cinnoxicam dan sudoxicam belum dipelajari secara menyeluruh.