A scintigraphic study was carried out to compare the lung deposition of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in healthy volunteers. Validation of Technetium-99m ((99m)Tc) radiolabeling of the budesonide/lactose blend used in the Clickhaler and excipient-free budesonide used in the Turbuhaler was carried out using a multistage liquid impinger, and compared with reference unlabeled devices. Budesonide was quantified using high-performance liquid chromatography and (99m)Tc by scintillation counting. The percentages (SD) of fine particles (<5.5 microm diameter) from radiolabeled and unlabeled devices were not significantly different (p > 0.05). Mean values for drug and radiolabel, respectively, were 34.6% (2.5) and 31.6% (3.8) for the Clickhaler, and 29.8% (5.5) and 31.4% (5 6) for the Turbuhaler. Fifteen healthy male volunteers received a single dose (2 x 200 microg actuations) from both devices in a double-blinded, double dummy, crossover study. During dosing, each inhalation maneuver was recorded using a computer-linked pressure transducer. To permit accurate determination of radiolabeled drug deposition, the lung margins of each volunteer were determined by Krypton-81m ((81m)Kr) gas imaging. Mean [SD] lung deposition for the Clickhaler (26.8% [6.8], RSD 25.2) was significantly greater (p < 0.001) than for the Turbuhaler (15.8% [6.6], RSD 42.2). Inspiratory flow rate parameters were similar for both devices with peak and mean values of 73 and 51 L/min for the Clickhaler, and 73 and 47 L/min for the Turbuhaler, respectively. These results indicate that, in healthy volunteers, budesonide lung deposition was higher and more consistent with the Clickhaler than with the Turbuhaler.

The results of this survey show that Xaluprine® has good overall acceptability in the paediatric population and suggests that Xaluprine® is an important, alternative, age-appropriate formulation of mercaptopurine.

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K252a, an inhibitor of trk phosphorylation and nerve growth factor signal transduction in Pci 2 cells, blocked nerve growth factor-induced responses in cultured adult rat dorsal root ganglion sensory neurones. The nerve growth factor-dependent appearance of capsaicin sensitivity and accumulation of the neuropeptide substance P were inhibited when dorsal root ganglion neurones were grown in the presence of low concentrations (100 nM) of K252a. At higher concentrations (3~tM), however, K252a stimulated the development of capsaicin sensitivity and the accumulation of substance P even in the absence of nerve growth factor. By using a wide dose range, therefore, we showed that K252a could either inhibit or mimic nerve growth factor's actions on sensory neurones. These results may explain the apparent paradox in the literature that some groups show a blocking effect of K252a on nerve growth factor-dependent survival of dorsal root ganglion sensory neurones, whereas others report that K252a can substitute for nerve growth factor or other trophic factors and promote neuronal survival. Key Words: Sensory neurones-Substance P-Capsaicin sensitivity-Nerve growth factor-K252a-Culture. J. Neurochem. 67,[345][346][347][348][349][350][351].