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Comparative Population Pharmacokinetic‐Pharmacodynamic Analysis for Piroxicam‐β‐Cyclodextrin and Piroxicam
Author(s) -
Wang Dan,
Miller Raymond,
Zheng Jenny,
Hu Chuanpu
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000004001110
Subject(s) - piroxicam , pharmacokinetics , medicine , pharmacodynamics , osteoarthritis , anesthesia , analgesic , pain relief , absorption (acoustics) , population , rheumatoid arthritis , plasma concentration , pharmacology , materials science , alternative medicine , environmental health , pathology , composite material
Piroxicam (Feldene®) is indicated for osteoarthritis and rheumatoid arthritis but not analgesia due to its delayed onset of pain relief. Piroxicam ‐β‐ cyclodextrin (PBCD) was developed for pain indication by virtue of the increased absorption rate of piroxicam. Forty‐eight patients received a single dose of PBCD or Feldene (10, 20, and 40 mg) in a randomized study, and piroxicam plasma concentration and pain relief were measured. The purpose of the study was to investigate the PK‐PD relationship of piroxicam, determine the optimal dose, and evaluate the effect of increased absorption rate on analgesic effect of piroxicam for the pain model studied. The pharmacokinetic data were best described by a two‐compartment model with first‐order absorption. The absorption rate of PBCD (5/h) was faster than Feldene (1.41/h). Pain relief was found to be increasing with drug concentration in a hypothetical effect compartment (E max model). The estimated half‐life of the equilibration between plasma and effect site was about 2.34 hours. Monte Carlo simulation showed that the time when at least 50% of the patients have a 75% probability of achieving meaningful pain relief (pain intensity difference (PID ≥ 1) for PBCD and Feldene at a dose of 20 mg was about 0.5 and 1.5 hours, respectively. PBCD demonstrated an advantage with an onset of pain relief 1 hour earlier than Feldene .