Enantiomer gastrointestinal absorption

The breakthrough in the development of quinolones came with the appearance of norfloxacin 6 [19], a second-generation quinolone which combined a 6-fluorine substituent with a piperazine ring in the 7-position of the basic compound. Additional quinolones then followed in rapid succession pefloxacin [20], enoxacin [21] and fleroxacin [22] (Fig. 14.5). Particular mention must be made of ciprofloxacin 8 [23-25], ofloxacin 5 [26,27] and its active enantiomer levofloxacin 7 [28]. These quinolones have a broad spectrum of activity, which also includes Gram-positive bacteria and Pseudomonas aeruginosa, as well as favorable pharmacokinetics. The rapid absorption of these compounds from the gastrointestinal tract and their effective tissue penetration also allows them to be used for the treatment of systemic infections. 

The amount of verapamil presented to the liver, and its effective concentration in the region of the hepatic er zymes soon after oral dosing, are related to the rate at which verapamO is absorbed from the gastrointestinal tract into the portal vein and to the flow rate of blood in the portal vein to the liver. For instance, by hypothesizing a Michaelis-Menten metabolic process, when the absorption rate is slow and concentrations in the portal vein and liver are low, the hepatic metabolism of both enantiomers will be approximately first-order. Under these conditions, the K S ratio of the umnetabolized enantiomers leaving the liver will be closely related to the ratio of the Michaelis-Menten saturation constants (K ) for the enantiomers. The observed more rapid metabolism of S-verapamil than R-verapamil (i.e., S-verapamil has the lower systemic concentrations) is consistent with the lower reported for S-verapamil (16). 

For the majority of drugs, absorption from the gastrointestinal tract occurs via passive processes that cannot distinguish between the enantiomers of a racemate. Additionally, there is no evidence that any of the antiasthma drugs are absorbed by a carrier mediated process thus stereoselectivity in the absorption of antiasthma agents currently used in clinical practice is not expected [115]. 

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