Does Chinese ethnicity affect the pharmacokinetics and pharmacodynamics ofangiotensin-converting enzyme inhibitors?

Information from clinical and pharmacokinetic studies of angiotensin-conver ting enzyme inhibitors (ACEIs) has come from subjects who are mostly male a nd Caucasian, but the use of ACEIs extends to populations worldwide. Signif icant differences between Chinese in general and male Caucasians have been demonstrated in the pharmacokinetics/dynamics of other drug classes that co uld have implications for the use of ACEIs in the Chinese population. These include: significant Chinese/Caucasian genetic variation in the renin-angi otensin system based on an insertion/deletion (O/D) polymorphism of the ACE gene; the genetic determination of plasma ACE activity in the Chinese popu lation; and genetic factors involving the disease substrate which may also influence the response to treatment. Oral and IV pharmacokinetic data from various studies of Chinese and Caucasian subjects are available for cilazap ril, fosinopril, and perindopril, and pharmacodynamic data are available fo r eight different ACEIs. Based on these data, there are few differences amo ng the pharmacokinetics of ACEIs between Chinese and Caucasians. Most ACEIs showed good blood pressure lowering efficacy in Chinese (benazepril, enala pril, fosinopril and spirapril), with perhaps less blood pressure lowering with cilazapril or a relatively shorter-term effect with cilazapril or peri ndopril compared to Caucasions. Chinese experience more cough from ACEIs (c aptopril and enalapril) than Caucasians, Data suggest that fosinopril may n ot induce cough in as many subjects as other ACEIs, and this seems to be tr ue of Chinese as well. The mechanism, currently unknown, could involve fosi nopril's dual elimination pathway (hepatic and renal), Pharmacokinetic data also support the use of fosinopril in congestive heart failure where elimi nation pathways may be impaired. In conclusion, ethnic differences between Chinese and Caucasians with respect to ACE and AGT gene polymorphism, which might be expected to differentially affect the action of ACEIs in these tw o ethnic groups, do not, in fact, have such an effect. Rather, differences among the ACEIs appear to be more important.