Search

AbstractAim: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 AUC0–t (23.9±8.26 μg.h.mL−1) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 μg.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.Conclusion: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 [ABSTRACT FROM AUTHOR]

Aim: To investigate the influence of omeprazole on the pharmacokinetics of domperidone given as free base and maleate salt. Methods: An open, randomized, 2-period crossover study with a washout period of 7 d was conducted in 10 healthy Chinese, male patients. In each study period, the patients were administered a single oral dose of 10 mg domperidone as free base or maleate salt on d 1, 20 mg omeprazole twice daily on d 2 and 3, and once on d 4. A single dose of 10 mg domperidone as free base or maleate salt was taken at 4 h after administration of omeprazole on d 4. Plasma samples were collected on d 1 and 4 after the administration of domperidone, and the plasma concentrations of domperidone were determined by a sensitive liquid chromatography-tandem mass spectrometry method. Results: For free-base domperidone, pretreatment with omeprazole resulted in a 16% decrease in maximum concentration (Cmax), compared with administration alone ( P < 0.05). However, for maleate salt, with the exception of an increase in t1/2, no pharmacokinetic parameters were significantly changed. When the free base and maleate salt were administered alone, no differences were found in any parameters between the 2 formulations. In contrast, when they were administered in the presence of omeprazole, the Cmax of domperidone given as free base was lower (25.9%) than that given as maleate salt ( P < 0.05). Conclusion: Pretreatment of omeprazole does not affect the absorption of domperidone maleate, but leads to a moderately decreased rate of absorption of the free base. [ABSTRACT FROM AUTHOR]

Aim: To investigate the biotransformation of metoprolol, a β1-cardioselective adrenoceptor antagonist, by filamentous fungus, and to compare the parallels between microbial transformation and mammalian metabolism. Methods: Five strains of Cunninghamella (Celegans AS 3.156, Celegans AS 3.2028, C echinulata AS 3.2004, C blakesleeana AS 3.153 and AS 3.910) were screened for the ability to transform metoprolol. The metabolites of metoprolol produced by C blakesleeana AS 3.153 were separated and assayed by liquid chromatography-tandem mass spectrometry (LC/MSn). The major metabolites were isolated by semipreparative HPLC and the structures were identified by a combination of LC/MSn and nuclear magnetic resonance analysis. Results: Metoprolol was transformed to 7 metabolites; 2 were identified as new metabolites and 5 were known metabolites in mammals. Conclusion: The microbial transformation of metoprolol was similar to the metabolism in mammals. The fungi belonging to Cunninghamella species could be used as complementary models for predicting in vivo metabolism and producing quantities of metabolite references for drugs like metoprolol. [ABSTRACT FROM AUTHOR]