Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs.
OBJECTIVE
The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs.


METHODS
The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program.


RESULTS
The pharmacokinetic results showed that AUC(0-t) (23.9+/-8.26 microg.h.mL(-1)) in plasma after oral administration was significantly higher than after transdermal delivery (1.00+/-0.43 microg.h.mL(-1)). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration.


CONCLUSIONS
The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.Acta Pharmacologica Sinica (2009) 30: 1060-1064; doi: 10.1038/aps.2009.73; published online 8 June 2009.
Yuan
Yue
Y
Shenyang Pharmaceutical University, Shenyang 110016, China.
Chen
Xiao-Yan
XY
Li
San-Ming
SM
Wei
Xiu-Yan
XY
Yao
Hui-Min
HM
Zhong
Da-Fang
DF
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D000077239:Meloxicam; D013582:Synovial Fluid / Q000378:metabolism; D013843:Thiazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam