Eichelbaum M
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, FRG.
Dev Pharmacol Ther. 1992;18(3-4):131-4.
The majority of synthetic drugs with chiral centers are administered as racemates. Thus chemically, and to an even greater extent biologically, a racemic drug is not a single compound, but a 50:50 mixture of two enantiomeric drugs. No generalization can be made concerning whether and to what extent the activity, in either qualitative or quantitative terms, differs between enantiomers. It is not unusual for the enantiomers of a drug to have a high degree of enantioselectivity for one action but no enantioselectivity for another action. For instance S-propranolol is at least two orders of magnitude more potent than R-propranolol with regard to beta-adrenoceptor antagonism. However, the two enantiomers are equipotent with regard to their membrane stabilizing effect. It is often overlooked that enantioselectivity in the activity of enantiomers as determined in vitro cannot be extrapolated to the in vivo situation since enantioselective drug disposition can lead to an enantiomer ratio in vivo which differs substantially from that in the dosage form administered. Enantioselectivity in drug disposition seems to be the rule rather than the exception and, depending on whether the active or less active enantiomer is preferentially affected, there may be amplification or attenuation of in vivo as compared to the in vitro drug potency.
大多数含有手性中心的合成药物都是以外消旋体的形式给药。因此，从化学角度来看，更从生物学角度来看，外消旋药物不是单一化合物，而是两种对映体药物各占50:50的混合物。关于对映体之间的活性在定性或定量方面是否存在差异以及差异程度如何，无法一概而论。一种药物的对映体对一种作用具有高度对映选择性而对另一种作用没有对映选择性的情况并不罕见。例如，在β-肾上腺素能受体拮抗作用方面，S-普萘洛尔的效力比R-普萘洛尔至少高两个数量级。然而，这两种对映体在膜稳定作用方面效力相当。人们常常忽略的是，体外测定的对映体活性中的对映选择性不能外推至体内情况，因为对映选择性药物处置可导致体内对映体比例与给药剂型中的比例有很大差异。药物处置中的对映选择性似乎是普遍规律而非例外情况，并且根据活性较强或较弱的对映体是否受到优先影响，与体外药物效力相比，体内可能会出现活性增强或减弱的情况。
