Analysis of Plasma Concentrations of Theophylline in Smoking and Nonsmoking Patients with Asthma

BACKGROUND: While dosing theophylline in asthmatics, we should consider that a lot of medicines, substances, conditions and diseases affect the clearance of theophylline, such as smoking, macrolide antibiotics, barbiturates, oral contraceptives, heart and liver insufficiency, alcohol, calcium-antagonists, pneumonia, viral infections, hypoxemia, etc.AIM: The aim of the study is to investigate the concentrations of theophylline during the day in smoking and nonsmoking patients with asthma.MATERIAL AND METHODS: We have estimated the concentrations of theophylline 6 times daily by the HPLC method (Keith Muir, J Chromatography) in 20 smoking and 20 nonsmoking asthmatic patients, who were treated with theophylline sustained-release tablets 175 mg twice daily.RESULTS: In the first group of 20 nonsmoking patients we obtained constant therapeutic and optimal concentrations of theophylline. In the second group of 20 smoking asthmatics the concentration of theophylline in plasma, in 8pm and 8am the next day was very low.CONCLUSION: Because in smokers we have increased clearance and the decreased half- life of theophylline, and in order to prevent the night time life-threatening attacks, it is necessary to recommend maximal doses of theophylline, especially in the evening. According to the study, dosage should be individualized in order to optimize the treatment based on the measurement of theophylline concentration in plasma.

Optimisation of handling, activation and assessment procedures for Bufo marinus spermatozoa

In the present study, we investigated handling, activation and assessment procedures for cane toad (Bufo marinus) spermatozoa. Optimisation of these techniques will facilitate the maintenance of sperm viability during cryopreservation and during in vitro fertilisation (IVF) techniques in reproduction technologies for endangered species. Spermatozoa were taken from testicular macerates and assessed using plasma membrane integrity assays (live/dead stains) and quantitative scores of motility parameters. In the assessment of sperm viability using live/dead stains, there were small but significant differences in the percentage of sperm from cryopreserved samples staining positive with propidium iodide, Hoechst H33258 and Trypan blue; these differences were not large and all stains performed acceptably. Spermatozoa were activated by dilution of testicular macerates in water at one of two dilution ratios (1 : 6 or 1 : 20) with or without 0.1–5.0 mm theophylline. Sperm plasma membrane integrity (unstained spermatozoa) was unaffected by either dilution ratio (osmolarity) or theophylline concentration. However, sperm motility was significantly affected by osmolarity and theophylline concentration. The stimulation of sperm motility increased with higher theophylline concentrations and these strongly interacted with lower osmolarities through a higher dilution ratio of sperm macerates with water. Spermatozoa were exposed to increasing centrifugation forces to determine tolerance to physical stresses encountered during washing procedures. Forces between 50 and 800g were associated with a significant reduction in motility (mean 56 ± 3% decreasing to 27 ± 3%), but did not affect staining. In conclusion, centrifugation should be minimised in anuran sperm washing procedures; osmotic shock associated with higher dilution ratios reduces the capacity of anuran sperm to achieve high percentages of motile sperm, leading to a likely trade-off between dilution required for activation and sperm motility to optimise IVF fertilisation rates; and optimal conditions for sperm motility after activation occur at lower dilutions of suspensions with 5.0 mm theophylline. The present study has improved protocols for the handling of anuran sperm during pre- and post-cryopreservation procedures.

Bioavailability of a New Sustained-Release Anhydrous Theophylline Product

The bioavailability of a new sustained-release anhydrous theophylline product (Theophylline Lavipharm®) was evaluated and compared with the bioavailability of a well-established product, Theodur®. Two groups of 12 healthy non-smokers were given single doses of 200 or 300 mg of each product and two groups of 12 patients with asthma or chronic obstructive lung disease were given doses of 200 or 300 mg of each product every 12 h for 5-day periods. The values of the area under the plasma theophylline concentration against time curve (AUC), the maximum plasma theophylline concentration ( Cmax) and the time taken to reach Cmax (Tmax) for the two products did not differ significantly in the healthy groups or in the patients. The minimum and the average plasma theophylline concentrations and the fluctuation index were also calculated for the patients and there were no significant differences between the values for the two products. The new anhydrous theophylline product, Theophylline Lavipharm®, appears to show very similar bioavailability to Theodur®. No adverse reactions to the new product were reported.