Strategy for NSAID administration to aspirin-intolerant asthmatics in combination with PGE2 analogue: a theoretical approach.

Aspirin-induced asthma (AIA) is a severe inflammatory disease, which affects aspirin-intolerant patients after ingestion of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). In this article, a mathematical model describing arachidonic acid metabolism and its interaction with NSAIDs, is used to study the strategy for safe managing of NSAIDs to AIA patients. Three different AIA patient populations are taken into consideration. First, the values of aspirin and ibuprofen limiting doses that might induce symptoms of AIA are calculated and compared to experimentally observed threshold doses to enlighten which AIA patient population is susceptible to aspirin and ibuprofen. Second, the methodology of NSAID administration is studied on AIA populations susceptible to aspirin and ibuprofen by using 1,000 mg dose of aspirin and 200 or 400 mg dose of ibuprofen followed by PGE(2) analogue dosing. Our model results show that successive doses of PGE(2) analogue applied at appropriate time after aspirin or ibuprofen ingestion would enable administration of both NSAIDs to AIA patients. PGE(2) analogue doses and the corresponding times of their applications are calculated. The model is also used to estimate the duration of symptoms of AIA for different aspirin and ibuprofen doses.

Role of expression of prostaglandin synthases 1 and 2 and leukotriene C4 synthase in aspirin-intolerant asthma: a theoretical study.

Altered expressions of the key enzymes in arachidonic acid (AA) metabolism, prostaglandin synthase 1 and 2 and cysteinyl leukotriene C(4) synthase, are of importance in understanding aspirin-induced asthma. We propose a mathematical model of AA metabolism and its interaction with non-steroidal anti-inflammatory drugs (NSAIDs). Model simulations depict the impact of modified expressions of the above enzymes on the time dependent synthesis of cysteinyl leukotrienes and anti-inflammatory prostaglandins before and during NSAID exposure in different model states describing healthy humans as well as aspirin-tolerant and -intolerant asthmatics. The results are compared and evaluated with experimental data taken from the literature. Our results identify the decreased expression of prostaglandin H synthase 1 and increased expression of leukotriene C(4) synthase as the key elements in AA metabolism that contribute to increased leukotriene C(4) and decreased anti-inflammatory prostaglandins after NSAID dosing in aspirin-intolerant patients. On the other hand, the decreased expression of prostaglandin H synthase 2 implies permanently increased leukotriene C(4) and lowers the sensitivity to increased drug doses. The model is used for identification of susceptible patient populations for aspirin and ibuprofen, and for identification of critical aspirin doses that might induce bronchoconstriction.

Quantitative high-performance thin-layer chromatographic analysis of ampicillin in human urine.

A quantitative high-performance thin-layer chromatographic (HPTLC) method was developed for the analysis of ampicillin in urine. A dioxane-water-n-butanol-formic acid mobile phase system and HPTLC Silica gel 60 F254 as stationary phase were used. Quantitation was realized on a Zeiss PMQ 2 densitometer connected to a Varian A-25 recorder and an Apple II microcomputer or alternatively with an HP 9830A computer and HP 9862A plotter. A good linear range of detection (0.05-1.00 micrograms) at 480 nm was obtained. Standard statistical methods demonstrated good reproducibility (coefficient of variation is not greater than 3%). The method is appropriate for ampicillin quality control and pharmacokinetic studies.