L/T ratio

The concept of the L T ratio in inhalation therapy is a useful one, where L represents the local or lung availability of an inhaled drug and T the total systemic availability. This ratio will be affected by differences in first-pass metabolism. Another important variable that determines the L T ratio is the inhalation device. The L T ratio for budesonide is 0.66-0.85, depending on the method of inhalation (12). 

Another way of describing the L T ratio concept is that of pulmonary targeting. Drug properties that improve pulmonary targeting include slow absorption from the lungs, low oral systemic availability, and rapid systemic clearance. 

The third halogenative Ramberg-Backlund reaction is the Vedejs modification.16 He treated substrate 14 with NaH and C2CU in DME at room temperature and obtained alkene 15 in l.T ratio of E/Z. However, the Vedejs modification, albeit mild, is limited to sulfones in which the a-position bears a single hydrogen, an ester, and another substituent as exemplified by transformation 16W. 16 It does not work for simple, unactivated sulfones. 

IX. Lung Versus Total Bloavallabillty Ratio (L/T Ratio)... 

It is possible to evaluate the balance between pulmonary bioavailabiUty and systemic bioavailability if the following data are known retention of the drug in the inhaler, the percentage pulmonary and oropharyngeal deposition of the drug, the degree of Gl absorption, and the inactivation by the first-pass metaboUsm. From these data the L/T ratio (L = local bioavailability T = systemic bioavailabiUty) can be derived. 

Calculations have shown that for terbutaline, the L/T ratio averages 0.55 for a pMDI and 0.81 for Turbuhaler (108). For salbutamoL the L/T ratio averages 0.35 for pMDI, 0.15 for Rotahaler, 0.24 for Diskhaler, and 0.45 for Turbuhaler (108). The differences in value between salbutamol and terbutaline are a reflection of inherent differences in Gl absorption and first-pass metabolism between these drngs. 

A higher L/T ratio will always indicate a more favorable ratio with respect to the balance between desired and undesired effect resulting from a good targeting abiUty of the combination of substance and device, or from a low contribution of the GI tract. It may be a guide in the choice between devices containing the same the substance. A high L/T ratio also impUes that it is the pulmonary bioavailabiUty that determines the systanic activity. 

The clinical relevance of L/T ratio, a theoretical concept, is, however, less clear. Indeed, the L/T ratio is useful only in comparing the same drug substance in different inhaler devices. Comparisons between drugs should not be made, as different substances may differ in terms of relative activities in lungs and systemic circulation. For example, inhaled glucocorticosteroids, such as fluticasone, with minimal GI bioavailabiUty and hence a very high I/T ratio, have been shown to exert systemic effects (51). The L/T ratio should thus always be verified clini-... 

The thickness and the L/t ratio of the outer steps should be less than or equal to the respective values of any inner step. 

The outer steps of any adherend should not have an excessive L/t ratio to ensure that it does not become overloaded by the higher-than-average load transfer near the ends of the overlap. 

The increase in the overlap length from the L/t value of 5 to 25 typically doubled the joint efficiency, as shown in Figures 6 and 7. It should be realised, however, that this occurs only within this specific range of the L/t ratios. A similar increase from 25 to 125 would produce practically no increase in the joint strength. 

---